tbuckley/cabot-search huggingface dataset:
Normal human intestinal B lymphocytes. Increased activation compared with peripheral blood.
Authors: M G Peters, H Secrist, K R Anders, G S Nash, S R Rich, R P MacDermott
Journal: Journal of Clinical Investigation (1989)

The state of activation of normal human intestinal mononuclear cells obtained from transplant donors was studied. Compared with PBMC, freshly isolated intestinal mononuclear cells expressed significantly more cell surface activation antigens on both B and T lymphocytes. Intestinal mononuclear cells contained significant numbers of immunoglobulin secreting cells immediately after cell separation. This population included CD5-positive B cells that secreted predominantly IgA. Cells from the large bowel consistently revealed higher numbers of IgA secreting cells than cells from the small bowel. Thus, intestinal B cells are markedly activated in vivo compared with PBMC and this increased activation correlates with increased spontaneous antibody secretion. B cells from the large intestine are more highly activated and secrete more antibody than do cells from the small intestine. The intestinal lamina propria lymphoid compartment exhibits a heightened state of activation that may be important for its distinct role in mucosal defense.
COOPERATION BETWEEN CD4<sup>+</sup>AND CD8<sup>+</sup>T CELLS: When, Where, and How
Authors: Flora Castellino, Ronald N. Germain
Journal: Annual Review of Immunology (2006)

Concepts of cell-cell interactions in adaptive immunity have alternated between the simple and the complex. The notion that one population of small, circulating lymphocytes is responsible for adaptive immunity was sequentially supplanted by the concept of separate T and B lymphocyte populations that cooperate to produce IgG antibody responses, by a three-cell model in which a myeloid APC initiates these cooperative lymphoid responses, by the recognition of T cell subsets, and by the idea that CD8 + T cell subset responses to graft antigens depend on CD4 + T cell subset activity. Simplicity was reintroduced with the revelation that CD8 + T cells can act independently of CD4 + T cells against acute viral infections. The pendulum has swung again toward complexity with recognition of the distinct and conjoint contributions of innate stimuli, APCs, NK and NKT cells, Tregs, and CD4 + helper T cells to CD8 + T cell behavior during acute and chronic infections or as memory cells. The renewed appreciation that multiple, sometimes rare cell types must communicate during cell-mediated immune responses has led to questions about how such interactions are orchestrated within organized lymphoid tissues. We review recent advances in deciphering the specific contribution of CD4 + T cells to physiologically useful CD8 + T cell responses, the signals involved in producing acute effectors versus long-lived memory cells, and the mechanisms underlying the cell-cell associations involved in delivery of such signals. We propose a model based on these new findings that may serve as a general paradigm for cellular interactions that occur in an inflamed lymph node during the initiation of immune responses.
Revealing Tumor Immunity after Hematopoietic Stem Cell Transplantation
Authors: Catherine J. Wu, Jerome Ritz
Journal: Clinical Cancer Research (2009)

Allogeneic hematopoietic stem cell transplantation is currently the most effective method for inducing tumor immunity. However, the diversity of target antigens recognized by donor T cells has not been established. New studies show that tumor-reactive T cells are directed against diverse tumor-specific targets as well as minor histocompatibility antigens.
Synaptic Vesicle Protein 2B Is Expressed in Podocyte, and Its Expression Is Altered in Proteinuric Glomeruli
Authors: Naoko Miyauchi, Akira Saito, Tamaki Karasawa, Yutaka Harita, Koichi Suzuki, Hiroko Koike, Gi Dong Han, Fujio Shimizu, Hiroshi Kawachi
Journal: Journal of the American Society of Nephrology (2006)

Synaptic vesicle protein 2B (SV2B) was identified by the subtraction hybridization technique as a molecule of which mRNA expression was decreased in puromycin aminonucleoside (PAN) nephropathy by glomerular cDNA subtraction assay. The expression of SV2B was detected in glomerular lysate with Western blot analysis. Dual-labeling immunofluorescence studies with glomerular cell markers demonstrated that SV2B is expressed in glomerular visceral epithelial cells (podocytes). The expression of SV2B is detected also in cultured podocyte and in human kidney section as podocytic pattern. The decrease of SV2B mRNA was already detected before the onset of proteinuria in PAN nephropathy. The mRNA expression of SV2B clearly is altered not only in PAN nephropathy but also in another proteinuric state that is caused by an antibody against nephrin, a functional molecule of the slit diaphragm. The decreased intensity in SV2B staining was already detected before the peak of proteinuria in both models with immunofluorescence study. A reduced amount of SV2B was detected in both models also with Western blot analysis. CD2AP, another functional molecule of the slit diaphragm, was observed in cytoplasm, including the processes area of the cultured podocyte, and when the podocyte was treated with small interfering RNA for SV2B, CD2AP staining at the process area was not detected. These results suggest that SV2B is a functional molecule of podocyte, and SV2B may play a role in the expression and proper localization of CD2AP.
Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis
Authors: Joanne Katz, Anne CC Lee, Naoko Kozuki, Joy E Lawn, Simon Cousens, Hannah Blencowe, Majid Ezzati, Zulfiqar A Bhutta, Tanya Marchant, Barbara A Willey, Linda Adair, Fernando Barros, Abdullah H Baqui, Parul Christian, Wafaie Fawzi, Rogelio Gonzalez, Jean Humphrey, Lieven Huybregts, Patrick Kolsteren, Aroonsri Mongkolchati, Luke C Mullany, Richard Ndyomugyenyi, Jyh Kae Nien, David Osrin, Dominique Roberfroid, Ayesha Sania, Christentze Schmiegelow, Mariangela F Silveira, James Tielsch, Anjana Vaidya, Sithembiso C Velaphi, Cesar G Victora, Deborah Watson-Jones, Robert E Black
Journal: The Lancet (2013)
A Novel Serotonin Blocker, Sarpogrelate, Increases Circulating Adiponectin Levels in Diabetic Patients With Arteriosclerosis Obliterans
Authors: Jun’ichi Yamakawa, Takashi Takahashi, Tohoru Itoh, Kazuya Kusaka, Ken Kawaura, Xin Qui Wang, Tsugiyasu Kanda
Journal: Diabetes Care (2003)

The recent article by Tsunekawa et al. (1) demonstrates that adiponectin plays an important role in improving insulin resistance. Inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), are associated with the risk of development of arteriosclerosis among both diabetic and nondiabetic patients (2).

Low plasma adiponectin concentrations were clinically observed in patients with type 2 diabetes (3). These findings suggest that adiponectin might have anti-inflammatory properties and might act as an endogenous modulator for the development of obesity-related diseases.

Serotonin is a naturally occurring vasoactive substance and has also been involved with vascular inflammation leading to the atherosclerosis (4). Sarpogrelate hydrochloride is a serotonin 2A receptor antagonist and is clinically used for the cutaneous ulcer and ischemic change resulting from the arteriosclerosis.

Cryesthesia was defined …
National Patient Safety Agency: combining stories with statistics to minimise harm
Authors: T. Lamont, J. Scarpello
Journal: BMJ (2009)

In a busy endoscopy clinic, you draw up part of a high strength midazolam ampoule and realise that you have oversedated the patient. The patient has been harmed. What stops you reporting it? What would prevent it from happening again in your trust or elsewhere?

An article about avoiding midazolam overdose is the first in a series of BMJ summaries of recommendations to improve patients’ safety, based on reports of safety concerns, incident analysis, and other evidence.1 The midazolam article is from the National Patient Safety Agency (NPSA) in England and Wales, which each week receives reports from healthcare professionals of serious incidents that have the potential for serious harm.2 This article is a summary of the agency’s rapid response report (RRR) on midazolam overdose. RRRs are one-page notices with clear recommendations for actions that will reduce risks to patients, issued to all relevant NHS organisations in England and Wales, from hospitals to primary care organisations (www.nrls.npsa.nhs.uk/resources/type/alerts/).

Previous national safety interventions took time to develop3 and proved challenging to implement.4 And so over the past two years, the NPSA has developed RRRs as more timely alerts to staff about new or under-recognised risks. The trigger for an RRR is reported deaths or serious events that may be seen as “one-off” events by local organisations but which at a national level indicate to the agency that system weaknesses exist for which fixes are available that could benefit all trusts. RRRs are issued in England through the Department of Health’s central alerting system (https://www.cas.dh.gov.uk), and organisations are required to act on these within a …
Maintenance Treatment of Pernicious Anaemia by Massive Parenteral Doses of Vitamin B12 at Intervals of Twelve Weeks
Authors: J. D. Kinloch
Journal: BMJ (1960)

antibodies to the recipient's tissue cells by the marrow graft.That this has not been found in the present case may be due to the close relationship, and the fact that the donor is known to possess all the blood-group antigens found in the patient.Summary A patient is described who suffered from acute bone- marrow failure due to chemotherapy for Hodgkin's disease.She was treated with a bone-marrow transfusion from her sister.Evidence is presented to show that the bone-marrow graft survived for-more than six months, responsible for the production of an increasing proportion (now 24%) of the patient's erythrocytes.A skin graft was undertaken between the donor of the marrow and the patient, but it was not successful.[ADDENDUM.-Werepeated the haematological investigation on this patient on September 26, 1959.Rh-positive cells are still present in her circulation.Titration studies indicate that approximately 40% of her circulating erythrocytes are Rh-positive.Woodruff and Lennox have recently published (Lancet, 1959, 2, 476) further details of the results of the skin grafts in blood-group chimeras.]
Neuropsychological Dysfunction in Antipsychotic-Naive First-Episode Unipolar Psychotic Depression
Authors: S. Kristian Hill, Matcheri S. Keshavan, Michael E. Thase, John A. Sweeney
Journal: American Journal of Psychiatry (2004)

The profile of neuropsychological impairment associated with unipolar psychotic depression remains unclear. The authors used a neuropsychological test battery to characterize the neuropsychiatric profile of patients with unipolar psychotic depression, relative to that of patients with nonpsychotic unipolar depression, patients with schizophrenia, and healthy comparison subjects.Study subjects included antipsychotic-naive patients with a first episode of psychotic unipolar depression (N=20), antipsychotic-naive and unmedicated patients with nonpsychotic unipolar depression (N=14), antipsychotic-naive patients with first-episode schizophrenia (N=86), and healthy volunteers (N=81). Groups were matched on age, sex, race, education, parental socioeconomic status, and estimated premorbid intelligence. Psychotic patients were followed clinically for 2 years to confirm diagnosis. All participants completed a standard neuropsychological battery, including tests of general intelligence, executive function, attention, verbal memory, motor skills, and visual-spatial perception.Patients with psychotic depression had a pattern of neuropsychological dysfunction that was similar to but less severe than that of patients with schizophrenia. In contrast, patients with nonpsychotic unipolar depression had a neuropsychological profile that was similar to that of healthy individuals but that included mild dysfunction on tests of attention. Neuropsychological test performance was generally independent of acute clinical symptoms, but some pairwise group differences were attenuated by covariation for symptom severity.The similar neuropsychological profiles for schizophrenia and psychotic depression suggest that these psychotic disorders may have common pathophysiological features. The dramatic differences in performance between the patients with psychotic depression and those with nonpsychotic depression point to a marked distinction in neurocognitive function associated with the expression of psychosis in depressed patients.
Short-term effects of transdermal nicotine on acute tissue plasminogen activator release in vivo in man
Authors: M Pellegrini
Journal: Cardiovascular Research (2001)

Cigarette smoking impairs peripheral endothelium-dependent vasodilatation and acute tissue plasminogen activator (t-PA) release in man. The aim of the study was to determine if this endothelial dysfunction is, in part, mediated by the effects of nicotine.Blood flow and plasma fibrinolytic factors were measured in both forearms of eight healthy male non-smokers during unilateral brachial artery infusion of the endothelium-dependent vasodilator, substance P (2 to 8 pmol/min). Endothelium-independent vasodilatation was assessed using intra-arterial infusion of sodium nitroprusside (2 to 8 microg/min). Subjects attended after 7 days treatment with transdermal nicotine or placebo in a double blind randomised crossover design.Plasma cotinine concentrations rose from 0.4+/-0.1 (placebo) to 125+/-25 ng/ml during nicotine administration (P<0.001). On both treatment days, substance P caused dose-dependent increases in blood flow and plasma t-PA antigen and activity concentrations (P<0.001 for all) but had no effect on plasma plasminogen activator inhibitor type 1 (PAI-1) concentrations. Compared with placebo, nicotine administration increased the substance-P-induced release of t-PA antigen and activity (P<0.05 for both) without an effect on endothelium-dependent or -independent vasodilatation.Short-term transdermal nicotine treatment does not affect endothelium-dependent vasomotion but does increase substance-P-induced t-PA release in vivo in man. This suggests that nicotine administration alters specific aspects of endothelial function and enhances the acute endogenous fibrinolytic capacity in vivo. The long-term effects of nicotine exposure, including the potential to cause depletion of endothelial t-PA stores, now needs to be assessed.
Endothelin-1 Stimulates Lymphatic Endothelial Cells and Lymphatic Vessels to Grow and Invade
Authors: Francesca Spinella, Emirena Garrafa, Valeriana Di Castro, Laura Rosanò, Maria Rita Nicotra, Arnaldo Caruso, Pier Giorgio Natali, Anna Bagnato
Journal: Cancer Research (2009)

The lymphatic vasculature is essential for tissue fluid homeostasis and cancer metastasis, although the molecular mechanisms involved remain poorly characterized. Endothelin-1 (ET-1) axis plays a crucial role in angiogenesis and tumorigenesis. Here, we first report that ET-1 acts as a lymphangiogenic mediator. We performed in vitro and in vivo studies and show that lymphatic endothelial cells produce ET-1, ET-3, and express the endothelin B receptor (ET(B)R). In these cells, ET-1 promotes proliferation, invasiveness, vascular-like structures formation, and phosphorylation of AKT and p42/44 mitogen-activated protein kinase through ET(B)R. In normoxic conditions, ET-1 is also able to up-regulate the expression of vascular endothelial growth factor (VEGF)-C, VEGF receptor-3, and VEGF-A, and to stimulate hypoxia-inducible factor (HIF)-1alpha expression similarly to hypoxia. Moreover, HIF-1alpha silencing by siRNA desensitizes VEGF-C and VEGF-A production in response to ET-1 or hypoxia, implicating HIF-1alpha/VEGF as downstream signaling molecules of ET-1 axis. Double immunofluorescence analysis of human lymph nodes reveals that lymphatic vessels express ET(B)R together with the lymphatic marker podoplanin. Furthermore, a Matrigel plug assay shows that ET-1 promotes the outgrowth of lymphatic vessels in vivo. ET(B)R blockade with the specific antagonist, BQ788, inhibits in vitro and in vivo ET-1-induced effects, demonstrating that ET-1 through ET(B)R directly regulates lymphatic vessel formation and by interacting with the HIF-1alpha-dependent machinery can amplify the VEGF-mediated lymphatic vascularization. Our results suggest that ET-1 axis is indeed a new player in lymphangiogenesis and that targeting pharmacologically ET(B)R and related signaling cascade may be therapeutically exploited in a variety of diseases including cancer.
“Cyst-like” structures within the ciliary shafts in children with bronchiectasis
Authors: M. Pifferi, A.M. Cangiotti, D. Caramella, A. Pietrobelli, V. Ragazzo, E. De Marco, P. Macchia, S. Cinti, A.L. Boner
Journal: European Respiratory Journal (2004)

"Cyst-like" structures within the ciliary shafts were considered in four adults as a primary defect involved in the development of bronchiectasis. In this study, the presence and the primary or secondary nature of this abnormality were assessed in children with bronchiectasis. High resolution computed tomography (HRCT) and nasal biopsies for motion analysis and transmission electron microscopy (TEM) evaluation of cilia were obtained in 45 children with recurrent lower airway infections and abnormal chest radiography. HRCT disclosed bronchiectasis in 35 out of 45 (77.8%) children and cyst-like structures were demonstrated with TEM in 29 out of 45 (64.4%) patients. Cyst-like structures were constantly associated with other ultrastructural abnormalities commonly observed in chronic inflammation, and were found both in subjects with primary and with secondary ciliary dyskinesia. When considering only patients with bronchiectasis, a significant correlation between prevalence of cyst-like structures and the severity of bronchiectasis was demonstrated. Follow-up (2-22 months) of seven patients demonstrated that in the five children with secondary dyskinesia, the ultrastructural defect completely disappeared and there was a small reduction in the abnormality in the two patients with primary dyskinesia. In contrast to one previous report, the reversibility of the defect suggests its secondary origin, which is most likely related to chronic airway inflammation.
Long-QT Syndrome-Associated Missense Mutations in the Pore Helix of the HERG Potassium Channel
Authors: Fu-De Huang, Jun Chen, Monica Lin, Mark T. Keating, Michael C. Sanguinetti
Journal: Circulation (2001)

Background Mutations in the human ether-à-go-go-related gene ( HERG ) cause chromosome 7-linked long-QT syndrome (LQTS), an inherited disorder of cardiac repolarization that predisposes affected individuals to arrhythmia and sudden death. Methods and Results Here, we characterize the physiological consequences of 3 LQTS-associated missense mutations (V612L, T613M, and L615V) located in the pore helix of the HERG channel subunit. Mutant HERG subunits were heterologously expressed in Xenopus oocytes alone or in combination with wild-type HERG subunits. Two-microelectrode voltage-clamp techniques were used to record currents, and a single oocyte chemiluminescence assay was used to assay surface expression of epitope-tagged subunits. When expressed alone, V612L and T613M HERG subunits did not induce detectable currents, and L615V induced very small currents. Coexpression of mutant and wild-type HERG subunits caused a dominant-negative effect that varied for each mutation. Conclusions These findings define the physiological consequences of mutations in HERG that cause LQTS and indicate the importance of the pore helix of HERG for normal channel function.
Influence of age and duration of follow-up on lung function after combined chemotherapy for Hodgkin's disease
Authors: BV Jensen, NL Carlsen, NI Nissen
Journal: European Respiratory Journal (1990)

Pulmonary function was studied in 48 patients 4-13 yrs after treatment for Hodgkin's disease with mantle-field irradiation followed by standard mechlorethamine, Oncovin, procarbazine and prednisone (MOPP) chemotherapy. The patients were found to have a restrictive lung disease suggestive of pulmonary fibrosis. Low age at therapy (less than or equal to 30 yrs, median 24 yrs) was associated with a significantly more pronounced restrictive lung function impairment than older age (greater than 30 yrs, median 40 yrs) suggesting a higher susceptibility to the pulmonary side-effects of therapy. In addition younger smokers had a significantly greater reduction in diffusion capacity and forced expiratory volume in one second than older smokers, suggesting a higher susceptibility to the additional adverse effect of smoking. With longer follow-up nonsmokers had an increase in static lung volumes. It is suggested that this may be the result of more frequent pulmonary infections in such patients as compared with the general population. However, the duration of follow-up was not associated with changes in other indices of lung function.
On the Development of Disturbances of Sensation in Diseases of the Spinal Cord
Authors: L. J. J. Muskens
Journal: BMJ (1899)

M nmz& r6o0i of the right hand on voluntary movement.The touch with the head of a pin recogniset on both lhanjds, but not quite so distinctly on the fingers of the right haud as on those of tle left.The sense of pain and temperature and the power of Iccalising tactile sensation not affected.Objects placed in the zight lhand (when the eyes were closed) were felt, but their nature 4was not recognised.The sense oI pressure (tested by weights) and the sense of passive movements and of position were lost in the right hand.Left hand not affected.Heart normal.CASE IV-M.H., female.Dilated heart, mitral systolic munnur.History of left-sided hemiplegia of sudden onset, complete recovery from the paralysis.Tactile and painful sensations recognised In the left hand quite well, but inability to tell the nature of objects placed in the hand, the eyes being closed.CASE v.-E.R., female, aged 37. Cardiac dilatation, mitral systolic murmur, right-sided hemiplegia of sudden onset; recovery almost com- plete, only the sliglhtest impairment of the grasp of the right hand remained; tactile and painful impressions recognised in the right hand quite well, but loss of the stereognostic sense.
Portable Oxygen Equipment and Walking-aid in Pulmonary Emphysema
Authors: E. J. M. Campbell
Journal: BMJ (1957)

BMRmH MEDICAL JOURNAL merely sedated.Overactive psychiatric patients showed some evidence of behaviour improvement.The observations are taken as indicating that 10-20% bemegride with barbiturate reduces or even prevents the development of coma or of prolonged sleep.The observations are tentatively presented for consideration in the treatment of patients in whom sleep treatment or prolonged sedation is desired but can be maintained only by the use of high barbiturate doses which, if given alone, involve the risk of barbiturate poisoning or other serious complications.
Peptides that form amyloid plaques in Alzheimer’s may be transmissible, study finds
Authors: Susan Mayor
Journal: BMJ (2015)

Amyloid β, the peptide that forms amyloid plaques in the brains of people with Alzheimer’s disease, may be transmissible through medical treatments such as blood products and surgical instruments, a small UK study published in Nature has shown.1

Researchers working on iatrogenic Creutzfeldt-Jakob disease (iCJD) unexpectedly found four autopsy cases with moderate to severe deposition of amyloid β in the grey matter of the brain typical of that seen in Alzheimer’s disease. They also found the peptide in the blood vessel walls deposited in a way that was characteristic of cerebral amyloid angiopathy.

The London based research group was working on an autopsy study of eight people aged 36 to 51 with iCJD, which was typically contracted by the use of human cadaveric pituitary derived growth hormone contaminated with prions. This treatment was withdrawn in 1985, but cases continue to emerge because of the prolonged incubation periods that can occur in human …