tbuckley/cabot-search huggingface dataset:
Increased lung neutrophil apoptosis and inflammation resolution
Authors: I. Moret, M. J. Lorenzo, B. Sarria, R. Menendez
Journal: European Respiratory Journal (2012)

From the authors:

We would like to thank C.G.A. Persson and L. Uller for their interesting observations and suggestions concerning our recently published article [1]. Also, we would like to comment the issues they have raised.

As they point out, we performed our study in patients (and controls), using blood and bronchoalveolar lavage (BAL) neutrophils for in vivo / ex vivo experiments. We did not include tissue samples due to the difficulty of obtaining them, just as C.G.A. Persson and L. Uller acknowledge. We analysed neutrophils from BAL fluid from non-responding community-acquired pneumonia (NCAP) patients to whom bronchoscopy was indicated and had signed informed consent. Bronchoscopy has the advantage of being a technique that is able to sample around 106 alveoli and, in addition, it is indicated for patients with NCAP [2]. All this could give relevant …
Circulating immune complexes in patients with fulminant hepatic failure.
Authors: J Canalese, R J Wyke, D Vergani, A L Eddleston, R Williams
Journal: Gut (1981)

Circulating immune complexes were found in 15 of 16 patients with fulminant hepatic failure due to viral hepatitis and all of six patients who had had halothane anaesthesia; however, they were found in only five of 32 patients with paracetamol-induced hepatic necrosis. The levels of circulating immune complexes were not related to the severity of the clinical course, development of renal failure, final outcome, or severity of hypocomplementaemia. All the patients had depressed reticuloendothelial function as assessed by the clearance of 125I microaggregated albumin. These findings show that circulating immune complexes in fulminant hepatic failure are not simply a reflection of an immune response to liver antigens released as a result of the hepatic necrosis; nor are they a reflection of the failure of the reticuloendothelial system. This supports the view that circulating immune complexes are associated with immune mediated liver injury and may contribute to the process.
Both intrathymic and peripheral selection modulate the differential expression of V beta 5 among CD4+ and CD8+ T cells.
Authors: P J Fink, K Swan, G Turk, M W Moore, F R Carbone
Journal: The Journal of Experimental Medicine (1992)

Murine T cells expressing V beta 5 are characterized by (a) intrathymic deletion in the presence of I-E and products of endogenous mouse mammary tumor viruses, and (b) a greater representation in CD8+ relative to CD4+ peripheral T cells, thought to be due to more efficient intrathymic positive selection on class I rather than class II major histocompatibility complex antigens. We have engineered mice that are transgenic for a rearranged gene encoding a V beta 5+ beta chain of the T cell receptor for antigen. Deletion is not predicted in I-E- V beta 5+ transgenic mice, and until the age of 2 wk, the CD4/CD8 ratio of peripheral T cells is &amp;gt; 3:1 and indistinguishable between transgenic and nontransgenic mice. Transgenic mice then show a rapid, age-dependent decline in the ratio of CD4+ to CD8+ T cells in the lymphoid periphery, reaching a low of 1:10 by 7 mo of age. Furthermore, the percent of peripheral CD4+ cells that express the transgene drops with age, reaching a low of about 60% at 7 mo, while the percent of CD8+ cells that express V beta 5 remains greater than 95% at all ages. The lymphoid periphery is implicated in this selection against CD4+ V beta 5+ T cells as it occurs more rapidly in thymectomized transgenic mice, and can be delayed in mice whose peripheral T cells are replaced by recent thymic emigrants after depletion by in vivo treatment with anti-Thy-1 antibodies. These results indicate that the relative expression of V beta 5 in T cell subsets can be influenced not only intrathymically in I-E+ V beta 5+ transgenic mice, but also by events in the periphery, in the absence of I-E expression.
Basic training in ophthalmology
Authors: S. Cook
Journal: Journal of the Royal Society of Medicine (2004)

The paper by Professor Fielder and his colleagues (April 2004 JRSM1) provides information that confirms the experience of the Training Committee of the Royal College of Ophthalmologists from our programme of hospital inspections. The issue is complex, and even within a hospital that is well disposed towards surgical training for senior house officers (SHOs) the experience can vary within any given year depending upon the SHOs in post. In general terms, around half of the units we inspect provide reasonable training to their trainees at the time of inspection. The bulk of the remaining units are capable of providing appropriate training experience if they are pressurized into monitoring the training experience of their SHOs and submitting their returns.

Modernizing Medical Careers offers ophthalmology an opportunity to restructure our training programmes. Ophthalmology will require approximately 50% of the current number of SHOs if we intend to move towards a run-through training grade. The principal issue is the service workload being undertaken throughout the UK by the remaining 50% of SHOs. This is the problem that needs to be addressed. If the number of SHOs in training were reduced, one would anticipate that a better quality of training would be available to this lesser number of trainees. It is also of great importance that consultant trainers are given sufficient time within their working week to engage with trainees and that the culture of the NHS is not driven by service alone.
Size of tonsils in recurrent tonsillitis
Authors: L. G McClymont, A C Thompson
Journal: BMJ (1989)

many forms of non-accidental injury may do this either directly by the injury itself or by indirect means, the same result can occur from other conditions.These are most commonly epileptic fits, but haemorrhages can also occur in asphyxia and thoracic compression, especially if there are associated blood coagulation defects.While retinal haemorrhages may well be an associated sign of non-accidental injury, they should not be taken as being pathognomonic ofthis cause.
Review of<i>Eye Movement Disorders in Clinical Practice</i>
Authors: Shin C. Beh
Journal: JAMA Neurology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Viral DNA detection and <i>RAS</i> mutations in actinic keratosis and nonmelanoma skin cancers
Authors: A. Zaravinos, P. Kanellou, D.A. Spandidos
Journal: British Journal of Dermatology (2009)

Actinic keratosis (AK) is a well-established precancerous skin lesion that has the potential to progress to squamous cell carcinoma (SCC). Basal cell carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely metastasizes. A number of viruses have been proposed to play a role in the development of nonmelanoma skin cancers (NMSC), but the most plausible evidence to date suggests that cutaneous human papillomavirus (HPV) is the key instigating factor.To evaluate the prevalence of HPV, cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) and investigate their relationship with the presence of RAS gene mutations in cutaneous lesions obtained from nonimmunosuppressed patients.HPV, CMV, HSV and EBV detection was performed using polymerase chain reaction (PCR) in skin biopsies (26 AK, 12 SCC and 15 BCC samples) that were collected from immunocompetent patients. The RAS mutation incidence was also investigated in all cutaneous lesions by use of PCR/restriction fragment length polymorphism and direct DNA sequencing.Seventeen out of 53 (32%) skin lesions were found to be positive for HPV DNA. The highest incidences of HPV infection were five of 15 (33%) in BCC and four of 12 (33%) in SCC specimens. The HPV incidence was eight of 26 (31%) in AK and eight of 53 (15%) in normal skin tissue. Twelve out of 53 (23%) skin lesions were CMV-positive. The highest incidence of CMV infection was six of 15 (40%), observed in BCC specimens. The CMV incidence was two of 26 (8%) in AK and four of 12 (33%) in SCC. No normal skin biopsy was found to be positive for CMV. All cutaneous samples were negative for HSV and EBV DNA, as assessed by our PCR-based assays. Only three samples, one AK (4%), one BCC (6%) and one SCC (8%), were found to carry a G>T transversion at the second position of HRAS codon 12. Both HRAS mutant SCC and BCC biopsies were HPV- and CMV-positive, as well.HPV DNA is detected in NMSC, AK and normal skin biopsies. Our results also indicate that CMV is involved in NMSC at higher levels than in premalignant lesions, whereas the virus was not detected in normal skin biopsies. HSV and EBV do not appear to be involved in the pathogenesis of cutaneous lesions. Moreover, we suggest that the HRAS codon 12 mutation is not a very common event in AK or NMSC. Finally, both viral infection and HRAS activation appear to represent independent factors in the aetiology of NMSC, samples of which were obtained from immunocompetent patients.
RECEPTORS FOR HLA CLASS-I MOLECULES IN HUMAN NATURAL KILLER CELLS
Authors: Alessandro Moretta, Cristina Bottino, Massimo Vitale, Daniela Pende, Roberto Biassoni, Maria Cristina Mingari, Lorenzo Moretta
Journal: Annual Review of Immunology (1996)

▪ Abstract Natural killer cells are likely to play an important role in the host defenses because they kill virally infected or tumor cells but spare normal self-cells. The molecular mechanism that explains why NK cells do not kill indiscriminately has recently been elucidated. It is due to several specialized receptors that recognize major histocompatibility complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more class I alleles leads to NK-mediated target cell lysis. During NK cell development, the class I–specific receptors have adapted to self–class I molecules on which they recognize epitopes shared by groups of class I alleles. As such, they may fail to recognize either self-molecules that bound unusual peptides or allogeneic class I molecules unrelated to self-alleles. Different types of receptors specific for groups of HLA-C or HLA-B alleles have been identified. While in most instances, they function as inhibiting receptors, an activating form of the HLA-C-specific receptors has been identified in some donors. Molecular cloning of HLA-C- and HLA-B-specific receptors has revealed new members of the immunoglobulin superfamily with two or three Ig-like domains, respectively, in their extracellular portion. While the inhibiting form is characterized by a long cytoplasmic tail associated with a nonpolar transmembrane portion, the activating one has a short tail associated with a Lys-containing transmembrane portion. Thus, these human NK receptors are different from the murine Ly49 that is a type II transmembrane protein characterized by a C type lectin domain. A subset of cytolytic T lymphocytes expresses NK-type class I–specific receptors. These receptors exert an inhibiting activity on T cell receptor–mediated functions and offer a valuable model to analyze the regulatory mechanisms involved in receptor-mediated cell activation and inactivation.
GRP94 (gp96) and GRP94 <i>N</i>-Terminal Geldanamycin Binding Domain Elicit Tissue Nonrestricted Tumor Suppression
Authors: Julie C. Baker-LePain, Marcella Sarzotti, Timothy A. Fields, Chuan-Yuan Li, Christopher V. Nicchitta
Journal: The Journal of Experimental Medicine (2002)

In chemical carcinogenesis models, GRP94 (gp96) elicits tumor-specific protective immunity. The tumor specificity of this response is thought to reflect immune responses to GRP94-bound peptide antigens, the cohort of which uniquely identifies the GRP94 tissue of origin. In this study, we examined the apparent tissue restriction of GRP94-elicited protective immunity in a 4T1 mammary carcinoma model. We report that the vaccination of BALB/c mice with irradiated fibroblasts expressing a secretory form of GRP94 markedly suppressed 4T1 tumor growth and metastasis. In addition, vaccination with irradiated cells secreting the GRP94 NH2-terminal geldanamycin-binding domain (NTD), a region lacking canonical peptide-binding motifs, yielded a similar suppression of tumor growth and metastatic progression. Conditioned media from cultures of GRP94 or GRP94 NTD-secreting fibroblasts elicited the up-regulation of major histocompatibility complex class II and CD86 in dendritic cell cultures, consistent with a natural adjuvant function for GRP94 and the GRP94 NTD. Based on these findings, we propose that GRP94-elicited tumor suppression can occur independent of the GRP94 tissue of origin and suggest a primary role for GRP4 natural adjuvant function in antitumor immune responses.
Characterization of high density lipoproteins in patients heterozygous for Tangier disease.
Authors: G Assmann, O Simantke, H E Schaefer, E Smootz
Journal: Journal of Clinical Investigation (1977)

In this study a large family group affectd with Tangier disease has been investigated. Besides two homozygous propositi, several heterozygous patients have been identified on the basis of quantitative measurements of high density lipoproteins and their constitutive polypeptides. By a variety of quantitative immunological methods, such as one-dimensional Laurell eletrophoresis, two-dimensional immunoelectrophoresis, and double-antibody radioimmunoassay, the total amount of apoprotein A-I and apoprotein A-I contained in the serum of heterozygous patients and the distribution of these A apoproteins among serum lipoproteins have been determined. The molar ration of apoprotein A-I and apoprotein A-II contained in high density lipoproteins of heterozygous patients did not significantly differ from that of control preparations, although the total mass of high density lipoproteins was reduced by approximately 50%. The elution profile of high density lipoproteins from agarose columns and their morphological appearance, as ascertained by electron microscopy, were similar to control preparations. In addition to the quantitative alterations of serum lipoproteins, lipid storage in histiocytes of the rectal mucosa obtained from heterozygous patients has been documented. It is concluded that patients heterozygous for Tangier disease have normal high density lipoproteins in circulation, the total mass of which is reduced by approximately 50%.
Relation Between Mural Force and Pressure in the Left Ventricle of the Dog
Authors: Lloyd L. Hefner, L. Thomas Sheffield, Glenn C. Cobbs, Willem Klip
Journal: Circulation Research (1962)

An investigation of the relationship in the dog between left ventricular pressure, left ventricular size, and total longitudinal force developed by the wall of the left ventricle is reported. This study required the development of a method for recording the force needed to keep together the two edges of a slit in the ventricle. Such a method is described, and samples of the force curves are shown, the general features of which are consistent with predictions from the physiology of muscle strips. The net force which the muscle fibers develop perpendicular to a given plane through the ventricle is almost identical to the product of the intracavitary pressure and the area of the cavity included in the plane. This relationship holds true regardless of the thickness of the wall or the shape of the ventricle.
Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance
Authors: Karsten Sydow, Andreas Daiber, Matthias Oelze, Zhiqiang Chen, Michael August, Maria Wendt, Volker Ullrich, Alexander Mülsch, Eberhard Schulz, John F. Keaney, Jonathan S. Stamler, Thomas Münzel
Journal: Journal of Clinical Investigation (2004)

Recent studies suggest that mitochondrial aldehyde dehydrogenase (ALDH-2) plays a central role in the process of nitroglycerin (glyceryl trinitrate, GTN) biotransformation in vivo and that its inhibition accounts for mechanism-based tolerance in vitro. The extent to which ALDH-2 contributes to GTN tolerance (impaired relaxation to GTN) and cross-tolerance (impaired endothelium-dependent relaxation) in vivo remain to be elucidated. Rats were treated for three days with GTN. Infusions were accompanied by decreases in vascular ALDH-2 activity, GTN biotransformation, and cGMP-dependent kinase (cGK-I) activity. Further, whereas in control vessels, multiple inhibitors and substrates of ALDH-2 reduced both GTN-stimulation of cGKI and GTN-induced vasodilation, these agents had little effect on tolerant vessels. A state of functional tolerance (in the GTN/cGMP pathway) was recapitulated in cultured endothelial cells by knocking down mitochondrial DNA (rho(0) cells). In addition, GTN increased the production of reactive oxygen species (ROS) by mitochondria, and these increases were associated with impaired relaxation to acetylcholine. Finally, antioxidants/reductants decreased mitochondrial ROS production and restored ALDH-2 activity. These observations suggest that nitrate tolerance is mediated, at least in significant part, by inhibition of vascular ALDH-2 and that mitochondrial ROS contribute to this inhibition. Thus, GTN tolerance may be viewed as a metabolic syndrome characterized by mitochondrial dysfunction.
Widespread aggregation of mutant VAPB associated with ALS does not cause motor neuron degeneration or modulate mutant SOD1 aggregation and toxicity in mice
Authors: Linghua Qiu, Tao Qiao, Melissa Beers, Weijia Tan, Hongyan Wang, Bin Yang, Zuoshang Xu
Journal: Molecular Neurodegeneration (2013)

A proline-to-serine substitution at position-56 (P56S) of vesicle-associated membrane protein-associated protein B (VAPB) causes a form of dominantly inherited motor neuron disease (MND), including typical and atypical amyotrophic lateral sclerosis (ALS) and a mild late-onset spinal muscular atrophy (SMA). VAPB is an integral endoplasmic reticulum (ER) protein and has been implicated in various cellular processes, including ER stress, the unfolded protein response (UPR) and Ca2+ homeostasis. However, it is unclear how the P56S mutation leads to neurodegeneration and muscle atrophy in patients. The formation of abnormal VAPB-positive inclusions by mutant VAPB suggests a possible toxic gain of function as an underlying mechanism. Furthermore, the amount of VAPB protein is reported to be reduced in sporadic ALS patients and mutant SOD1G93A mice, leading to the hypothesis that wild type VAPB plays a role in the pathogenesis of ALS without VAPB mutations. To investigate the pathogenic mechanism in vivo, we generated human wild type (wtVAPB) and mutant VAPB (muVAPB) transgenic mice that expressed the transgenes broadly in the CNS. We observed robust VAPB-positive aggregates in the spinal cord of muVAPB transgenic mice. However, we failed to find an impairment of motor function and motor neuron degeneration. We also did not detect any change in the endogenous VAPB level or evidence for induction of the unfolded protein response (UPR) and coaggregation of VAPA with muVAPB. Furthermore, we crossed these VAPB transgenic mice with mice that express mutant SOD1G93A and develop motor neuron degeneration. Overexpression of neither wtVAPB nor muVAPB modulated the protein aggregation and disease progression in the SOD1G93A mice. Overexpression of VAPBP56S mutant to approximately two-fold of the endogenous VAPB in mouse spinal cord produced abundant VAPB aggregates but was not sufficient to cause motor dysfunction or motor neuron degeneration. Furthermore, overexpression of either muVAPB or wtVAPB does not modulate the course of ALS in SOD1G93A mice. These results suggest that changes in wild type VAPB do not play a significant role in ALS cases that are not caused by VAPB mutations. Furthermore, these results suggest that muVAPB aggregates are innocuous and do not cause motor neuron degeneration by a gain-of-toxicity, and therefore, a loss of function may be the underlying mechanism.
Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. I. Rejection by syngeneic mice.
Authors: C Uyttenhove, J Van Snick, T Boon
Journal: The Journal of Experimental Medicine (1980)

We have reported that it is possible to obtain variants that are incapable of forming progressive tumour in syngeneic mice (tum-) by mutagenesis and cloning of a teratocarcinoma and a Lewis lung carcinoma cell line. These observations were extended to the ascitic P815 mastocytoma of mouse strain DB/2. After a treatment with the mutagen N-methyl-N"-nitro-N-nitrosoguanidine, we obtained a high frequency (14%) of tum- clones. A colony assay indicated that after a period of rapid multiplication extending to approximately 10 d after injection, the P815 tum- cells were rejected by a process that was usually completed by day 15. No rejection was observed in sublethally irradiated animals. The immunological nature of the rejection of the P815 variants was further inferred because, upon rejection, the mice acquired a radioresistant specific protection that could be transferred adoptively with spleen cells. Cross-immunization patterns demonstrated the presence of singular antigenic specificities on three of the five variants that were examined. In addition, a common antigen was found on all the tum- variants and the original cells that were capable of forming progressive tumors in syngeneic mice (tum+). Mice injected with tum- cells were significantly protected against a tum+ challenge, even though no significant protection was generated by irradiated tum+ cells. A study of the T lymphocyte-mediated cytolysis against the P815 variants described here is presented in the accompanying report (9).