tbuckley/cabot-search huggingface dataset:
Antigen Receptor–Induced Activation and Cytoskeletal Rearrangement Are Impaired in Wiskott-Aldrich Syndrome Protein–Deficient Lymphocytes
Authors: Jinyi Zhang, Amro Shehabeldin, Luis A.G. da Cruz, Jeffrey Butler, Ally-Khan Somani, Mary McGavin, Ivona Kozieradzki, Antonio O. dos Santos, Andras Nagy, Sergio Grinstein, Josef M. Penninger, Katherine A. Siminovitch
Journal: The Journal of Experimental Medicine (1999)

The Wiskott-Aldrich syndrome protein (WASp) has been implicated in modulation of lymphocyte activation and cytoskeletal reorganization. To address the mechanisms whereby WASp subserves such functions, we have examined WASp roles in lymphocyte development and activation using mice carrying a WAS null allele (WAS−/−). Enumeration of hemopoietic cells in these animals revealed total numbers of thymocytes, peripheral B and T lymphocytes, and platelets to be significantly diminished relative to wild-type mice. In the thymus, this abnormality was associated with impaired progression from the CD44−CD25+ to the CD44−CD25− stage of differentiation. WASp-deficient thymocytes and T cells also exhibited impaired proliferation and interleukin (IL)-2 production in response to T cell antigen receptor (TCR) stimulation, but proliferated normally in response to phorbol ester/ionomycin. This defect in TCR signaling was associated with a reduction in TCR-evoked upregulation of the early activation marker CD69 and in TCR-triggered apoptosis. While induction of TCR-ζ, ZAP70, and total protein tyrosine phosphorylation as well as mitogen-activated protein kinase (MAPK) and stress-activated protein/c-Jun NH2-terminal kinase (SAPK/JNK) activation appeared normal in TCR-stimulated WAS−/− cells, TCR-evoked increases in intracellular calcium concentration were decreased in WASp-deficient relative to wild-type cells. WAS−/− lymphocytes also manifested a marked reduction in actin polymerization and both antigen receptor capping and endocytosis after TCR stimulation, whereas WAS−/− neutrophils exhibited reduced phagocytic activity. Together, these results provide evidence of roles for WASp in driving lymphocyte development, as well as in the translation of antigen receptor stimulation to proliferative or apoptotic responses, cytokine production, and cytoskeletal rearrangement. The data also reveal a role for WASp in modulating endocytosis and phagocytosis and, accordingly, suggest that the immune deficit conferred by WASp deficiency reflects the disruption of a broad range of cellular behaviors.
Intravenous Iron Exacerbates Oxidative DNA Damage in Peripheral Blood Lymphocytes in Chronic Hemodialysis Patients
Authors: Ko-Lin Kuo, Szu-Chun Hung, Yau-Huei Wei, Der-Cherng Tarng
Journal: Journal of the American Society of Nephrology (2008)

Patients undergoing maintenance hemodialysis have elevated markers of oxidative stress, but the reasons for this are not fully understood. Intravenous administration of iron, which many of these patients receive, may provoke the generation of bioactive iron, which enhances oxidative stress and lipid peroxidation. In this study, 110 hemodialysis patients were randomly assigned to five groups that were administered single intravenous doses of iron sucrose, ranging from 20 to 500 mg. A time- and dosage-dependent rise in lymphocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in lymphocyte DNA, a marker of oxidative DNA damage, with a significant increase at 2 h after intravenous iron of > or = 200 mg (P < 0.05). Four weeks later, patients were randomly assigned to weekly iron sucrose (100 mg of elemental iron) or saline for 12 wk, and 89 patients completed the study. Mean lymphocyte 8-OHdG content was significantly higher in patients receiving intravenous iron compared with control subjects (P < 0.05), especially in those with ferritin levels > 500 microg/L. In addition, flow cytometric techniques revealed increased production of reactive oxygen species in lymphocytes among those treated with intravenous iron. Treatment with intravenous iron but not saline was also associated with decreased plasma ascorbate and alpha-tocopherol levels and increased oxidized glutathione/reduced glutathione ratio (P < 0.05). In summary, intravenous iron sucrose provokes oxidative damage to peripheral blood lymphocyte DNA in hemodialysis patients, especially among those with high levels of ferritin.
Symptom Scores and Delirium in Advanced Cancer
Authors: José-Javier de Arriba, Cristina Nerín, María Carmen Ortiz, María del Soto Sesma, Silvestre Beltrán, Beatriz Vila
Journal: Journal of Clinical Oncology (2011)

In the interesting article by Seow et al 1 regarding the trajectory of symptom scores and performance status during the last months of life, an important issue is missed.More than 80% of patients with advanced cancer can develop delirium in the last days before death, and delirium is present in 26% to 44% of patients at the time of admission to an acute care hospital or palliative care unit. 2 If a patient is cognitively impaired, or for other reasons cannot participate in the symptom assessment, the Edmonton Symptom Assessment System (ESAS) is completed by the caregiver or professional.In that case, the subjective symptom scales (depression, anxiety, tiredness, and well-being) are left blank. 3eow et al states, "Scores were reported by the patient (ESAS) or provider (PPS [Palliative Performance Scale]) during visits to the cancer center or the home."If all of the ESAS were completed by the patient, we can deduce that a number of patients with delirium had to be excluded.It would be interesting to know if screening for delirium was performed, what tool was used, and how many patients were excluded for this reason.
Monoamine Oxidase Inhibitors Potentiate the Effects of Deep Brain Stimulation
Authors: Clement Hamani, Peter Giacobbe, Mustansir Diwan, Eliane S. Balbino, Junchao Tong, Alanna Bridgman, Nir Lipsman, Andres M. Lozano, Sidney H. Kennedy, José N. Nobrega
Journal: American Journal of Psychiatry (2012)

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Pyoderma gangrenosum in a child with congenital partial deficiency of leucocyte adherence glycoproteins
Authors: None Bedlow, None Davies, None Moss, None Rebuck, None Finn, None Marsden
Journal: British Journal of Dermatology (1998)

Congenital deficiency of β2 integrin leucocyte adhesion molecules is a rare immunodeficiency and is often fatal. Neutrophils are unable to bind to ligands on the endothelium, and so cannot leave the circulation during inflammation or infection. When leucocyte adhesion deficiency (LAD) is caused by abnormally low expression of β2 integrins, it is termed LAD type 1. We describe a 5‐year‐old girl with a history of recurrent bacterial infections since early childhood who developed necrotic skin ulcers resembling pyoderma gangrenosum and a persistent circulating neutrophilia. Histologically, the lesions showed deep ulceration with a diffuse lymphohistiocytic infiltrate, but with a relative sparsity of neutrophils. Subsequent investigation revealed a complete absence of CD11a/CD18 β2 integrins on the surface of the patient's neutrophils, confirming the diagnosis of LAD type 1. The ulcers responded to treatment with oral prednisolone and colchicine.
Bortezomib Plus CHOP-Rituximab for Previously Untreated Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma
Authors: Jia Ruan, Peter Martin, Richard R. Furman, Shing M. Lee, Ken Cheung, Julie M. Vose, Ann LaCasce, Julia Morrison, Rebecca Elstrom, Scott Ely, Amy Chadburn, Ethel Cesarman, Morton Coleman, John P. Leonard
Journal: Journal of Clinical Oncology (2010)

The proteasome inhibitor bortezomib may enhance activity of chemoimmunotherapy in lymphoma. We evaluated dose-escalated bortezomib plus standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (R) in patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).Seventy-six subjects with untreated DLBCL (n = 40) and MCL (n = 36) received standard CHOP every 21 days (CHOP-21) with R plus bortezomib at 0.7 mg/m(2) (n = 4), 1.0 mg/m(2) (n = 9), or 1.3 mg/m(2) (n = 63) on days 1 and 4 for six cycles.Median age was 63 years (range, 20 to 87), and International Prognostic Index (IPI) scores were generally unfavorable (39% with IPI of 2, and 49% with IPI of 3 to 5), as were Mantle Cell Lymphoma International Prognostic Index scores in patients with MCL (28% intermediate risk and 39% high risk). Toxicity was manageable, including neuropathy in 49 subjects (8% grade 2 and 4% grade 3) and grade 3/4 anemia (13%), neutropenia (41%), and thrombocytopenia (25%). For DLBCL, the evaluable overall response rate (ORR) was 100% with 86% complete response (CR)/CR unconfirmed (CRu; n = 35). Intent-to-treat (ITT, n = 40) ORR was 88% with 75% CR/CRu, 2-year progression-free survival (PFS) of 64% (95% CI, 47% to 77%) and 2-year overall survival (OS) of 70% (95% CI, 53% to 82%). For MCL, the evaluable ORR was 91% with 72% CR/CRu (n = 32). The ITT (n = 36) ORR was 81% with 64% CR/CRu, 2-year PFS 44% (95% CI, 27% to 60%) and 2-year OS 86% (95% CI, 70% to 94%). IPI and MIPI correlated with survival in DLBCL and MCL, respectively. Unlike in DLBCL treated with R-CHOP alone, nongerminal center B cell (non-GCB) and GCB subtypes had similar outcomes.Bortezomib with R-CHOP-21 can be safely administered and may enhance outcomes, particularly in non-GCB DLBCL, justifying randomized studies.
Hairdressing is associated with scalp disease in African schoolchildren
Authors: N.P. Khumalo, S. Jessop, F. Gumedze, R. Ehrlich
Journal: British Journal of Dermatology (2007)

Anecdotal reports suggest that certain disorders are common in African hair and may be associated with hairstyles.A cross-sectional study of 1042 schoolchildren was performed to test this hypothesis.A questionnaire was administered and scalp examinations performed, after ethics approval.Participants included 45% boys and 55% girls. The majority of boys, 72.8%, kept natural hair with frequent haircuts (within 4 weeks). The prevalence of acne (folliculitis) keloidalis nuchae (AKN) was 0.67% in the whole group and highest (4.7%) in boys in the final year of high school, all of whom had frequent haircuts. The majority of girls (78.4%) had chemically relaxed hair, which was usually combed back or tied in ponytails, vs. 8.6% of boys. Traction alopecia (TA) was significantly more common with relaxed than natural hair, with an overall prevalence of 9.4% (98 of 1042) and of 17.1% in girls, in whom it increased with age from 8.6% in the first year of school to 21.7% in the last year of high school. The proportion with TA in participants with a history of braids on natural hair was lower (22.9%), but not significantly, than among those with a history of braids on relaxed hair (32.1%). No cases of central centrifugal cicatricial alopecia were identified.We found associations between hairstyle and disease in our population of schoolchildren. AKN appears to be associated with frequently cut natural hair and TA with relaxed hair. These associations need further study for purposes of disease prevention.
A palmar epidermoid cyst, showing histological features suggestive of eccrine duct origin, developing after a bee-sting
Authors: K. Egawa, H. Kitasato, T. Ono
Journal: British Journal of Dermatology (2000)

Sir, Palmar and plantar epidermoid cysts have been described as being caused by implantation of epidermal fragments into the dermis as a result of a penetrating or blunt injury.1 However, Egawa observed that eccrine sweat ducts were frequently found in and/or connecting with palmoplantar epidermoid cysts and therefore proposed the alternative pathogenetic hypothesis that palmoplantar epidermoid cysts may develop from eccrine ducts,2 and that human papillomaviruses (HPVs) may partly play a role in their pathogenesis.3 A 64‐year‐old male first noticed an asymptomatic nodule on the volar aspect of the ring‐finger of his left hand 3 months before presentation and 6 months after suffering an injury from a sting of a honeybee at the same site. The sting produced immediate burning pain followed by an intense, local, erythematous reaction with swelling and urticaria, but when this acute phase of inflammation diminished, he noticed a fragment of the sting of the honeybee left at the site. Six months later, a miliary‐sized nodule appeared and gradually enlarged at the same site. Clinically, the nodule was smooth‐surfaced, dome‐shaped, and 8 mm in diameter. The nodule was excised with the provisional diagnosis of a foreign body granuloma reaction.
Use of tiotropium Respimat Soft Mist Inhaler<i>versus</i>HandiHaler and mortality in patients with COPD
Authors: Katia M.C. Verhamme, Ana Afonso, Silvana Romio, Bruno C. Stricker, Guy G.O. Brusselle, Miriam C.J.M. Sturkenboom
Journal: European Respiratory Journal (2013)

Tiotropium, a long-acting anticholinergic, is delivered <i>via</i> HandiHaler or <i>via</i> Respimat. Randomised controlled trials suggest that use of tiotropium Respimat increases the risk of dying. We compared the risk of mortality between tiotropium Respimat <i>versus</i> HandiHaler. Within the Integrated Primary Care Information database, we defined a source population of patients, aged ≥40 years, with ≥1 year of follow-up. Based on prescription data, we defined episodes of tiotropium use (Respimat or HandiHaler). The risk of mortality, within these episodes, was calculated using a Cox proportional hazard regression analysis. From the source population, 11 287 patients provided 24 522 episodes of tiotropium use. 496 patients died while being exposed to HandiHaler or Respimat. Use of Respimat was associated with almost 30% increased risk of dying (adjusted HR 1.27, 95% CI 1.03–1.57) with the highest risk for cardiovascular/cerebrovascular death (adjusted HR 1.56, 95% CI 1.08–2.25). The risk was higher in patients with co-existing cardiovascular disease (adjusted HR 1.36, 95% CI 1.07–1.73) than in patients without (adjusted HR 1.02, 95% CI 0.61–1.71). Use of tiotropium Respimat was associated with an almost 30% increase of mortality compared with HandiHaler and the association was the strongest for cardiovascular/cerebrovascular death. It is unclear whether this association is causal or due to residual confounding by chronic obstructive pulmonary disease severity.
Treatment of Syphilis
Authors: Meredith E. Clement, N. Lance Okeke, Charles B. Hicks
Journal: JAMA (2014)

The incidence of syphilis in the United States is increasing; it is estimated that more than 55,000 new infections will occur in 2014. Treatment regimens are controversial, especially in specific populations, and assessing treatment response based on serology remains a challenge.To review evidence regarding penicillin and nonpenicillin regimens, implications of the "serofast state," and treatment of specific populations including those with neurosyphilis or human immunodeficiency virus (HIV) infection and pregnant women.We searched MEDLINE for English-language human treatment studies dating from January 1965 until July 2014. The American Heart Association classification system was used to rate quality of evidence.We included 102 articles in our review, consisting of randomized trials, meta-analyses, and cohort studies. Case reports and small series were excluded unless they were the only studies providing evidence for a specific treatment strategy. We included 11 randomized trials. Evidence regarding penicillin and nonpenicillin regimens was reviewed from studies involving 11,102 patients. Data on the treatment of early syphilis support the use of a single intramuscular injection of 2.4 million U of benzathine penicillin G, with studies reporting 90% to 100% treatment success rates. The value of multiple-dose treatment of early syphilis is uncertain, especially in HIV-infected individuals. Less evidence is available regarding therapy for late and late latent syphilis. Following treatment, nontreponemal serologic titers should decline in a stable pattern, but a significant proportion of patients may remain seropositive (the "serofast state"). Serologic response to treatment should be evident by 6 months in early syphilis but is generally slower (12-24 months) for latent syphilis. Evidence defining treatment for HIV-infected persons and for pregnant women is limited, but available data support penicillin as first-line therapy.The mainstay of syphilis treatment is parenteral penicillin G despite the relatively modest clinical trial data that support its use.
The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells.
Authors: Ada Girnita, Charlotta All-Ericsson, Mario A Economou, Kristina Astr√∂m, Magnus Axelson, Stefan Seregard, Olle Larsson, Leonard Girnita
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Uveal melanoma has a high mortality rate due to a high incidence of metastasis (up to 50%), which preferentially occurs in the liver. Conventional chemotherapy, being the only therapeutic option today against metastatic uveal melanoma, has not proved to be effective. Therefore, new molecular targets important for malignant phenotype of uveal melanoma have to be found to design efficient pharmacologic agents. EXPERIMENTAL DESIGN: We previously reported data indicating that the insulin-like growth factor-1 receptor (IGF-IR) is a metastasis predictor as well as a therapeutic target for uveal melanoma. In the present study, we made use of the cyclolignan picropodophyllin (PPP), which is an inhibitor of the IGF-IR. RESULTS: We showed that PPP efficiently blocks growth and viability of uveal melanoma cells in cultures and causes tumor regression in xenografted mice. In addition, treatment with PPP inhibited several mechanisms involved in metastasis, including tumor cell adhesion to extracellular matrix proteins, activity and expression of matrix metalloproteinase 2, and cell migration as well as invasion through basement membranes and endothelial cell layers. Furthermore, PPP significantly delayed establishment of uveal melanoma tumors and drastically reduced the incidence of liver metastasis in mice. CONCLUSIONS: Our data suggest that IGF-IR is crucial for growth and survival as well as invasion and metastasis of uveal melanoma cells. Targeting this receptor may therefore comprise a strategy to treat ongoing disease (today incurable) as well as a strategy to prevent development of metastases in patients with primary disease.
Activation of Adenosine 2A Receptors Preserves Structure and Function of Podocytes
Authors: Alaa S. Awad, Michael Rouse, Lixia Liu, Amy L. Vergis, Diane L. Rosin, Joel Linden, John R. Sedor, Mark D. Okusa
Journal: Journal of the American Society of Nephrology (2007)

Adenosine 2A receptor (A(2A)R) activation was recently shown to be renoprotective in diabetic nephropathy. A(2A)R are found in glomeruli and have been shown to associate with the podocyte cytoskeletal protein alpha-actinin-4, but the effect of their activation on podocyte structure and function is unknown. Podocyte injury was induced in C57BL/6 mice with puromycin aminonucleoside, and the selective A(2A)R agonist ATL313 was found to attenuate the resulting albuminuria and foot process fusion. The selective A(2A)R antagonist ZM241385 reversed the effects of ATL313. In vitro, A(2A)R mRNA and protein were expressed in a conditionally immortalized podocyte cell line, and A(2A)R-like immunoreactivity co-localized with the actin cytoskeleton. Treatment with ATL313 also blocked the increased podocyte permeability to albumin and disruption of the actin cytoskeleton that accompanied puromycin aminonucleoside-induced injury in vitro. ATL313 was ineffective, however, in the presence of the A(2A)R antagonist and in A(2A)R-deficient podocytes. It was concluded that A(2A)R activation reduces glomerular proteinuria, at least in part, by preserving the normal structure of podocyte foot processes, slit diaphragms, and actin cytoskeleton.
Studies of Cat Heart Muscle during Recovery after Prolonged Hypothermia
Authors: TADASI TAMAI, SHUNSUKE KAGIYAMA
Journal: Circulation Research (1968)

Cat heart muscles preserved in normal Tyrode's solution at 4°C for prolonged periods were investigated by recording the transmembrane potentials after rewarming to 37°C. The cell membranes were gradually hyperpolarized during rewarming, the maximum hyperpolarization being reached within a few hours. The amplitude of resting potentials obtained at a maximally hyperpolarized stage was largest for ventricular muscle that had been preserved for 20 hours at 4°C and for atrial muscle that had been preserved for about 50 hours at 4°C. The maximum potentials averaged 267.7 mv for the ventricles and 184.4 mv for the atria. KC1 at 10 x normal and epinephrine and norepinephrine in final concentrations of 2.5 x 10 -7 g/ml brought about a marked hyperpolarization of the cell membrane when the membrane potential of the muscles was declining. The cells of muscles loaded with Li had a greater than normal membrane potential for an hour during gradual equilibration over a range of 4 to 22°C before rewarming. When muscles were rewarmed to 37°C in Li-Tyrode's solution the membrane potential gradually decreased to 5 to 23 mv for the right atrium and 13 to 34 mv for the right ventricle. Ouabain 10 -5 and 10 -6 M abolished the hyperpolarization and subsequently depolarized the cell membrane. DNP (0.2 and 0.6 mM) and sodium azide (6 mM) also had an inhibiting effect on the hyperpolarization. The observations are consistent with a hypothesis of an electrogenic sodium pump, which produces hyperpolarization whose magnitude depends largely on the previous length of time the tissue was preserved in the hypothermic state.
Intercostal ancient schwannoma mimicking an apical lung tumour
Authors: F Petteruti, G De Luca, A Lerro, A Luciano, I Cozzolino, P Pepino
Journal: Thorax (2008)

A 56-year-old woman was admitted to our hospital with inspiratory dyspnoea, dry cough, vague right chest pain and right arm pain for 2 months. She denied tobacco use or asbestos exposure and had no significant medical or family history.

A chest radiograph highlighted extensive radiopacity involving the superior right lobe, the lateral view detailed the mass as being located in the posterior mediastinum. Chest …