tbuckley/cabot-search huggingface dataset:
Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-Ig.
Authors: D B Knoerzer, R W Karr, B D Schwartz, L J Mengle-Gaw
Journal: Journal of Clinical Investigation (1995)

Antigen-specific T cell activation requires two independent signalling events, one mediated through T cell receptor engagement by the antigen-presenting cell-expressed peptide/class II major histocompatibility complex, and the second through the cognate interactions of costimulatory molecules expressed on the T cell and antigen-presenting cell. There is evidence from in vitro and in vivo experimental systems suggesting that the CD28/B7 costimulatory pathway is crucial for induction of maximal T cell proliferation and T helper-B cell collaboration for IgG production. This pathway can be blocked by CTLA-4-Ig, a soluble form of CTLA-4 which binds with high avidity to the CD28 ligands, B7-1 and B7-2. Here, we show that CTLA-4-Ig treatment prevents clinical and histological manifestations of disease in a collagen-induced arthritis model of rheumatoid arthritis in the diabetes resistant BB/Wor rat, when therapy is initiated before immunization with bovine type II collagen (BIIC). Anti-BIIC antibody titers are reduced in CTLA-4-Ig-treated rats compared to diseased control animals. Histologically, joints from CTLA-4-Ig-treated animals show no histological abnormalities, in contrast to control antibody-treated animals, which show complete erosion of the articular cartilage and bone. Despite the efficacy of CTLA-4-Ig in preventing clinical and histological signs of arthritis and reducing antibody responses to BIIC, delayed type hypersensitivity responses to collagen 18 d or more after CTLA-4-Ig treatment ends are similar in CTLA-4-Ig-treated and untreated rats, suggesting that the prolonged disease suppression observed does not result from induction of T cell anergy.
Evaluation of Xpert MTB/RIF assay performance in diagnosing extrapulmonary tuberculosis among adults in a tertiary care centre in India
Authors: Surendra K. Sharma, Mikashmi Kohli, Jigyasa Chaubey, Raj Narayan Yadav, Rohini Sharma, Binit Kumar Singh, Vishnubhatla Sreenivas, Abhishek Sharma, Rohit Bhatia, Deepali Jain, V. Seenu, Anita Dhar, Manish Soneja
Journal: European Respiratory Journal (2014)

To the Editor: 

According to the World Health Organization Global Tuberculosis Report from 2013, there were 8.6 million incident tuberculosis (TB) cases globally and India alone contributed 26% to this global scenario [1]. Of the five countries with the largest number of TB incident cases in 2012, India tops the list [1]. Epidemiological data suggest that extrapulmonary TB (EPTB) constitutes about 15–20% of all TB cases, but among HIV-TB co-infection it accounts for 50% of the cases [2]. Out of 1 183 373 new TB cases notified globally, 234 029 (20%) were reported to be cases of EPTB [1].

Difficulty in sampling from the extrapulmonary sites and the paucibacillary nature of the specimens make EPTB a diagnostic challenge. Dependency on smear microscopy in these samples may lead to higher false negative rates due to the low sensitivity of this technique. Mycobacterium tuberculosis (MTB) culture is quite a protracted technique, requiring well-trained laboratory personnel, and delay in diagnosis can cause more harm as the treatment is often started empirically.

Rapid nucleic acid amplification tests are emerging extensively to provide better yield for rapid diagnosis of TB. The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is an automated, hemi-nested real-time PCR for detecting MTB complex and rifampin (RIF) resistance, which was initially evaluated for pulmonary specimens in large studies [3–5].

The present communication reports the performance of Xpert MTB/RIF in EPTB samples, with a large sample size from a single centre in a country with a high TB burden.

All EPTB samples from indoor as well as outdoor facilities of the All India Institute of Medical Sciences (AIIMS) hospital, New Delhi, India, were received in the Tuberculosis Laboratory (accredited Intermediate Reference Laboratory …
The Oculomotor System
Authors: Kenneth R. Magee
Journal: JAMA (1964)

This book contains the papers given at a symposium on the oculomotor system held in April, 1961, at Mt. Sinai Hospital, New York. The chapters are written by 29 authorities who present the results of their research into the oculomotor system from the neurological, psychological, and physiological standpoints. Four areas of research are stressed: (1) the anatomy of the oculomotor system; (2) electrophysiological studies of integration between visual, vestibular, and oculomotor systems; (3) psychological and physiological studies on the role of visual and vestibular functions in eye movements; and (4) clinical and pathological investigations of eye movement disorders in patients. Symposiums stress the interests of the participants, usually resulting in emphasis of certain areas while other areas are relatively neglected. Although a modicum of this criticism can be leveled against this text, the editor, a distinguished neurologist, has done an excellent job in organizing the symposium to provide complete coverage
Emotional Stress and Cardiac Disease
Authors: Arthur Bobruff
Journal: JAMA (1977)

To the Editor.—  The description by Drs Eliot and Forker (236:2325, 1976) is valuable in describing an important aspect of the complex interaction between emotion and cardiac diseases. It is not the absence of mention of the reverse relationship of   secondary to cardiac disease that concerns me.  The virtual dismissal, however, of the valuable assets of psychotherapy and psychopharmacology in treating emotional stress is a glaring omission, not to be ignored.  I am fully aware of the sentence,  the individual cannot talk frankly about the origin of his excessive emotional stress to his physician, he should find a proper outlet, such as his wife, his minister, or a group therapy situation.  If a patient does have difficulty in talking with one of his physicians, it is certainly possible that he may profit from working with a member of the medical profession who specializes in the treatment of
Lipoproteins containing apoprotein B are a major regulator of neutrophil responses to monosodium urate crystals.
Authors: R Terkeltaub, L K Curtiss, A J Tenner, M H Ginsberg
Journal: Journal of Clinical Investigation (1984)

The inflammatory response to intraarticular urate crystals is known to be variable in gouty arthritis. One source of variability may be the modulation of cellular responses by crystal-bound proteins. We have identified three apolipoproteins among the polypeptides bound to urate crystals exposed to plasma. Identification was first based on their coelectrophoresis with polypeptides from isolated lipoproteins and diminution in the protein coat of crystals exposed to lipoprotein-depleted plasma. The apoproteins were immunochemically identified by the Western blotting technique as apoprotein A-I, apoprotein B (apo B), and apoprotein E. Because neutrophils play a central role in acute gout, we investigated the potential effects of lipoproteins on neutrophil-urate crystal interactions. Plasma profoundly inhibited urate crystal-induced neutrophil luminol-dependent chemiluminescence (CL). Lipoprotein depletion by KBr density gradient centrifugation completely abrogated the inhibitory effect of plasma on urate-induced CL. The inhibitory activity of lipoprotein-depleted plasma was restored by adding back the d less than or equal to 1.25 g/cm3 lipoprotein fraction. Plasma also inhibited urate crystal-induced neutrophil superoxide generation and cytolysis (lactic dehydrogenase loss). This inhibition was significantly diminished by lipoprotein depletion, indicating that the lipoprotein effect was not limited to CL. Lipoprotein-depleted plasma reconstituted with very low, intermediate, and low density lipoproteins (LDL) inhibited crystal-induced CL. High density lipoprotein reconstitution was without effect. Immunodepletion from plasma of all apo B lipoproteins by agarose-bound apo B-specific antibody also removed all inhibitory activity for urate-induced CL. Thus, apo B lipoproteins were shown to be the inhibitory species in plasma. Binding of apo B lipoproteins to urate crystals and inhibition of CL was also seen in the absence of other plasma proteins. In addition, the binding of whole lipoprotein particles to the crystals was verified by detection of crystal-associated cholesterol in addition to the apoprotein. The effects of LDL on urate crystal-induced CL were stimulus specific. Coincubation of urate crystals and neutrophils in the presence of 10 micrograms/ml LDL resulted in 83% inhibition. In contrast, CL responses to a chemotactic hexapeptide, opsonized zymosan, and Staphylococcus aureus were not inhibited by LDL. The effects of depletion of apo B lipoproteins on plasma suppression of urate crystal-induced CL appeared to be unique. Plasma or sera depleted of other urate crystal-binding proteins including fibrinogen, fibronectin, C1q, and IgG retained virtually all their CL inhibitory activity. Lipoproteins containing apo B are thus a major regulator of neutrophil responses to urate crystals. These lipoproteins are present in variable concentration in synovial fluid and may exert an important influence on the course of gout.
Serological Responses and Clinical Reactions to Influenza Virus Vaccines
Authors: F. Himmelweit
Journal: BMJ (1960)

necessary to lay down the sequences of movement in advance.It is not known whether this neurocellular atrophy is a direct result of the ageing process or whether it is based on ischaemia.Biemond (1951) found disappear- ance of Purkinje cells as a minimal result in some cases of basilar artery thrombosis, and suggested that " slight interference with the circulation in the cerebellum mav lead to a local and perhaps also a more diffuse disappearance of the Purkinje cells."These observa- tions are particularly relevant in view of the fact that no less than 50% of the whole sample and 60% of those having drop-attacks were unable to throw their head back without immediate symptoms.Reasons have already been adduced for the view that this is based on temporary obstruction to one or both vertebral arteries facilitated by senile cervical osteoarthritis, and it fits in well with Kremer's (1958) suggestion that drop- attacks are based on transient changes in the blood- supply to the brain-stem.Relative ischaemia in the territory supplied by the vertebral and basilar arteries might also underlie the high incidence of abnormal plantar responses, and much of the vertigo of which old people complain so bitterly may have the same origin.It is suggested, therefore, that the general insecurity of postural control and the liability to fall which are characteristic of old age are based ultimately on a decline in the number of nerve cells in the brain-stem, cerebellum, and other centres-below that available for the maintenance of normal postural function in earlier life.The adverse effects of this cellular poverty will inevitably be accentuated by interference with the blood supply to the region which, in two ways, is particularly apt to happen in old age-by the liability of the vertebral arteries to temporary obstruction and the general proneness to phases of hypotension based on postural and other causes.Many intriguing problems remain; the drop-attack remains a remarkable event-from its instantaneous onset to its apparent path of recovery in some cases by the initiation, through pressure on the soles of the feet, of a reflex which seems hitherto to have belonged more to the province of neurophysiology than of clinical medicine.Therein, however, lies one of the fascinations of old age as a clinical study, for these phenomena have been uncovered because at this stage of life Nature resembles the engineer who may release the unexpected when he tests his materials to destruction.
Identification of Ezrin-Radixin-Moesin proteins as novel regulators of pathogenic B-cell receptor signaling and tumor growth in diffuse large B-cell lymphoma
Authors: D Pore, J Bodo, A Danda, D Yan, J G Phillips, D Lindner, B T Hill, M R Smith, E D Hsi, N Gupta
Journal: Leukemia (2015)
Enhanced Gene Delivery by Avidin-Displaying Baculovirus
Authors: Jani K Räty, Kari J Airenne, Ari T Marttila, Varpu Marjomäki, Vesa P Hytönen, Pauliina Lehtolainen, Olli H Laitinen, Anssi J Mähönen, Markku S Kulomaa, Seppo Ylä-Herttuala
Journal: Molecular Therapy (2003)

Flexible alteration of virus surface properties would be beneficial for enhanced and targeted gene delivery. A useful approach could be based on a high-affinity receptor–ligand pair, such as avidin and biotin. In this study, we have constructed an avidin-displaying baculovirus, Baavi. Avidin display was expected to enhance cell transduction due to the high positive charge of avidin in physiological pH and to provide a binding site for covering the virus with desired biotinylated ligands. Successful incorporation of avidin on the virus envelope was detected by immunoblotting and electron microscopy. Multiple biotin-binding sites per virus were detected with fluorescence-correlation spectroscopy and tight biotin binding was observed using an optical biosensor, IAsys. Baavi showed a 5-fold increase in transduction efficiency in rat malignant glioma cells (BT4C) and a 26-fold increase in rabbit aortic smooth muscle (RAASMC) cells compared to wild-type baculovirus. Enhanced transduction was also observed with biotinylated target cells. Biotinylated epidermal growth factor (EGF) enabled specific targeting of the virus with high efficiency to EGF receptor-expressing (SKOV-3) cells. An additional advantage of the avidin display was demonstrated with biotinylated paramagnetic particles, which enabled magnetic targeting. Altogether, we show that avidin display is a rapid and versatile method to improve viral properties for gene delivery.
Exercise Rehabilitation for Treatment of Claudication
Authors: Alan T. Hirsch, George Haidet, Mark A. Creager, William R. Hiatt, Judith G. Regensteiner, John P. Cooke
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The meta-analysis by Drs Gardner and Poehlman<sup>1</sup>serves a critical role in demonstrating the efficacy of exercise rehabilitation as a therapeutic modality for individuals with claudication. Heretofore, cost studies that have evaluated essentially all therapeutic modalities for claudication (whether exercise, angioplasty, or surgery) have been hampered by small sample size or the lack of a randomized, controlled study design. It should be noted that these past limitations have in part been ameliorated by two significant publications that were not included in the<i>JAMA</i>meta-analysis. A randomized controlled trial performed by Hiatt and colleagues<sup>2</sup>demonstrated that a 12-week supervised walking program was superior in improving exercise performance compared with a well-described control group, and further validated the use of a graded exercise treadmill protocol to assess functional limitations in patients with claudication. Another randomized trial performed by Creasy and colleagues<sup>3</sup>compared the relative efficacy of
#3539 NARROW BAND IMAGING WITH HIGH RESOLUTION BRONCHOVIDEOSCOPE: A NEW APPROACH TO VISUALISE ANGIOGENESIS IN SQUAMOUS CELL CARCINOMA OF THE LUNG
Authors: Johan Vansteenkiste, K Shibuya, T Nakajima, K Yasufuku, A Iyoda, M Suzuki, Y Sekine, T Iizasa, K Hiroshima
Journal: Journal of Thoracic Oncology (2007)
260 ABERRANT METHYLATION OF ONCOSUPPRESSOR GENES DETECTED IN THE PERIPHERAL BLOOD OF PATIENTS WITH CHRONIC HEPATITIS C AND HEPATOCELLULAR CARCINOMA
Authors: M. Sampietro Maurizio, A.L. Fracanzani, D. Tavazzi, A. Cespiati, C. Bertelli, D. Bignamini, L. Valenti, S.R. Fargion
Journal: Journal of Hepatology (2011)
Metabolic Control and Complications in Diabetic Patients
Authors: Richard M. Bergenstal
Journal: JAMA (1981)

Whether good metabolic control can delay or prevent long-term microvascular complications in diabetes remains to be proved in man, despite the accumulation of a substantial amount of evidence supporting this viewpoint.<sup>1,2</sup>The difficulty in obtaining conclusive data to answer this question in man is threefold. First, methods to quantitate accurately the degree of glucose control over a prolonged period have not been available, although the recent development of the glycosylated hemoglobin (Hb A<sub>1c</sub>) assay,<sup>3</sup>which reflects an integrated value of blood glucose over the preceding weeks to months, may partly solve this problem. The second difficulty has been the lack of reproducible and specific techniques to assess quantitatively specific diabetic complications at an early stage. However, advances are being made in this area.<sup>4</sup>Third, it has been almost impossible to maintain prolonged normoglycemia, which might be a necessary condition to prevent the development of diabetic complications,
Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats.
Authors: H Chiao, Y Kohda, P McLeroy, L Craig, I Housini, R A Star
Journal: Journal of Clinical Investigation (1997)

Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.
<i>Staphylococcus aureus</i> in nasal lavage and biopsy of patients with chronic rhinosinusitis
Authors: A. Niederfuhr, H. Kirsche, T. Deutschle, S. Poppert, H. Riechelmann, N. Wellinghausen
Journal: Allergy (2008)

Background: Staphylococcus aureus may play a relevant etiologic role in chronic rhinosinusitis (CRS) and may explain the T H2 shift observed in CRS with nasal polyps (CRSNP + ). Naturally occurring S. aureus small colony variants (SASCV) escape immune surveillance, antibiotic treatment and microbiologic routine diagnostic techniques. The frequency of S. aureus and SASCV in CRS patients and S. aureus ‐related effects on the local immune response should be prospectively investigated. Methods: Nasal lavages and mucosal biopsies of CRS patients were examined with bacterial culture suitable for detecting SASCV, real time PCR and fluorescence in situ hybridization. To assess the effects of S. aureus positivity, interleukin‐5 (IL‐5), interferon‐γ, total immunoglobulin E (IgE), eotaxin, granulocyte‐colony stimulating factor, and eosinophil cationic protein in nasal lavages were determined and gene transcription analysis of nasal biopsies from S. aureus positive and negative CRSNP + patients was performed. Results: Thirty‐one CRSNP + patients, 13 CRS patients without polyps, and 21 control patients were evaluated. Staphylococcus aureus was detected by any method in 25 patients (39%). Staphylococcus aureus detection rates did not differ between the three disease groups ( P = 0.3). Staphylococcus aureus small colony variants were not found. In nasal lavages, IL‐5 and total IgE levels were higher in CRSNP + patients than in CRSNP − patients or controls ( P &lt; 0.05). Staphylococcus aureus positivity did not influence biomarker concentrations in nasal lavages. Genes for T H2 cytokines were not differentially transcribed. Conclusions: We could not observe a higher prevalence of S. aureus in CRS patients with or without nasal polyps than in controls. We could not substantiate that S. aureus intensifies the T H2 shift in CRSNP + patients. Staphylococcus aureus small colony variants were not detected in any sample.
Evidence That Angiotensin II and Lipoxygenase Products Activate c-Jun NH <sub>2</sub> -Terminal Kinase
Authors: Yeshao Wen, Stephen Scott, Yaxia Liu, Noe Gonzales, Jerry L. Nadler
Journal: Circulation Research (1997)

Abstract The effect of angiotensin II (Ang II) to activate c-Jun amino-terminal kinase (JNK) was studied in a Chinese hamster ovary fibroblast cell line overexpressing the rat vascular type-1a Ang II receptor (CHO-AT 1a ). Ang II treatment induced a time-dependent activation of JNK. Ang II (10 −7 mol/L) activated JNK activity, with a peak at 30 minutes (9.39±2.52-fold, n=7, P &lt;.02 versus control), which was maintained until 3 hours (2.7±0.65-fold, n=3, P &lt;.02 versus control). Ang II–induced JNK activation at 30 minutes was inhibited by a specific lipoxygenase (LO) pathway inhibitor, cinnamyl-3,4-dihydroxy-α-cyanocinnamate (1 μmol/L) by 87.5% (n=4, P &lt;.01 versus Ang II–induced JNK activity). The direct addition of 12-HETE also induced a time-dependent JNK activation. 12-HETE (10 −7 mol/L) activated JNK activity, with a peak at 10 minutes (3.43±0.87-fold, n=6, P &lt;.02 versus control), which remained elevated until 1 hour. These results suggest that the LO pathway is a mediator of Ang II–induced JNK activation. 15-HETE can also activate JNK at 5 minutes, but this activity was reduced at 30 minutes and could not be seen at 1 hour, indicating that the time course was different from that seen with 12-HETE. N -Acetylcysteine (NAC), an antioxidant, was used to perturb intracellular reactive oxygen intermediate (ROI) levels to assess the role of endogenous ROIs in regulating JNK activity. Pretreatment of cells with 500 μmol/L NAC for 1 hour attenuated ≈50% of Ang II–induced JNK activation, suggesting that ROIs, at least partially, mediate Ang II–induced JNK activation. Furthermore, 12-HETE–induced JNK activation was reduced by ≈90% by NAC. Finally, pertussis toxin completely blocked 12-HETE–induced JNK activation, suggesting that G i -protein signaling participates in 12-HETE–induced effects. These results suggest that LO activation plays a role in mediating Ang II–induced JNK activation in part by altering the redox tone and G i -protein signaling of cells.