tbuckley/cabot-search huggingface dataset:
Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis.
Authors: S Shimoda, J Van de Water, A Ansari, M Nakamura, H Ishibashi, R L Coppel, J Lake, E B Keeffe, T E Roche, M E Gershwin
Journal: Journal of Clinical Investigation (1998)

The immunodominant antimitochondrial antibody response in patients with primary biliary cirrhosis (PBC) is directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Based on our earlier observations regarding peripheral blood mononuclear cell (PBMC) T cell epitopes, we reasoned that a comparative analysis of the precursor frequencies of PDC-E2 163-176-specific T cells isolated from PBMC, regional hepatic lymph nodes, and from the liver of PBC patients would provide insight regarding the role of T cells in PBC. Results showed a disease-specific 100-150-fold increase in the precursor frequency of PDC-E2 163-176-specific T cells in the hilar lymph nodes and liver when compared with PBMC from PBC patients. Interestingly, autoreactive T cells and autoantibodies from PBC patients both recognize the same dominant epitope. In addition, we demonstrated cross-reactivity of PDC-E2 peptide 163-176-specific T cell clones with PDC-E2 peptide 36-49 and OGDC-E2 peptide 100-113 thereby identifying a common T cell epitope "motif" ExETDK. The peptide 163-176-specific T cell clones also reacted with purified native PDC-E2, suggesting that this epitope is not a cryptic determinant. These data provide evidence for a major role for PDC-E2 peptide 163-176 and/or peptides bearing a similar motif in the pathogenesis of PBC.
Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection
Authors: Nabora Soledad Reyes de Mochel, Scott Seronello, Shelley Hsiuying Wang, Chieri Ito, Jasper Xi Zheng, Jake T. Liang, David J. Lambeth, Jinah Choi
Journal: Hepatology (2010)

Oxidative stress has been identified as a key mechanism of hepatitis C virus (HCV)–induced pathogenesis. Studies have suggested that HCV increases the generation of hydroxyl radical and peroxynitrite close to the cell nucleus, inflicting DNA damage, but the source of reactive oxygen species (ROS) remains incompletely characterized. We hypothesized that HCV increases the generation of superoxide and hydrogen peroxide close to the hepatocyte nucleus and that this source of ROS is reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase 4 (Nox4). Huh7 human hepatoma cells and telomerase-reconstituted primary human hepatocytes, transfected or infected with virus-producing HCV strains of genotypes 2a and 1b, were examined for messenger RNA (mRNA), protein, and subcellular localization of Nox proteins along with the human liver. We found that genotype 2a HCV induced persistent elevations of Nox1 and Nox4 mRNA and proteins in Huh7 cells. HCV genotype 1b likewise elevated the levels of Nox1 and Nox4 in telomerase-reconstituted primary human hepatocytes. Furthermore, Nox1 and Nox4 proteins were increased in HCV-infected human liver versus uninfected liver samples. Unlike Nox1, Nox4 was prominent in the nuclear compartment of these cells as well as the human liver, particularly in the presence of HCV. HCV-induced ROS and nuclear nitrotyrosine could be decreased with small interfering RNAs to Nox1 and Nox4. Finally, HCV increased the level of transforming growth factor beta 1 (TGFβ1). TGFβ1 could elevate Nox4 expression in the presence of infectious HCV, and HCV increased Nox4 at least in part through TGFβ1. Conclusion: HCV induced a persistent elevation of Nox1 and Nox4 and increased nuclear localization of Nox4 in hepatocytes in vitro and in the human liver. Hepatocyte Nox proteins are likely to act as a persistent, endogenous source of ROS during HCV-induced pathogenesis. Hepatology 2010
Letter: Exercise-induced asthma
Authors: M. Weinberger
Journal: JAMA (1976)

As Dr Gillette points out in the first paragraph of his letter, we referenced two previous studies in our article and confirmed, with our own work, that the addition of penicillin G procaine to penicillin G benzathine significantly alters the high incidence and severity of local reactions compared to that seen when the latter is given alone. The second paragraph of Dr Gillette's letter cautions that it would be unwise to infer that our treatment regimen containing 900,000 units of penicillin G benzathine and 300,000 units of penicillin G procaine in a 2-ml injection offered any other advantages. We made no such inferences. We clearly stated in our summary that (1) "although the procaine component does not hasten the resolution of signs and symptoms when compared to the benzathine component alone," (2) "it clears the throat of streptococci more rapidly," (3) "greatly decreases the incidences and severity of
Cumulative infectious burden (but not any single past infection) is interrelated with traditional risk factors to cause coronary artery disease
Authors: Einat Cotter-Metzkor, Ricardo Krakover, Gad Cotter, Miriam Ben-Yaakov, Tzilia Lazarovich, Zehava Chen-Levy, Ronit Zaidenstein, Shlomo Fytlovich, Ida Boldur, Ahuva Golik
Journal: Journal of the American College of Cardiology (2003)
Association of the Renin-Sodium Profile with the Risk of Myocardial Infarction in Patients with Hypertension
Authors: Michael H. Alderman, Shantha Madhavan, Wee L. Ooi, Hillel Cohen, Jean E. Sealey, John H. Laragh
Journal: New England Journal of Medicine (1991)

To test the prognostic value of plasma renin activity prospectively, we determined the pretreatment renin-sodium profile of 1717 subjects with mild-to-moderate hypertension (mean age, 53 years; 36 percent white; 67 percent men) in a systematic work-site treatment program.
Gingival and Periungual Vasculopathy of Juvenile Dermatomyositis
Authors: Lisa G. Rider, Jane C. Atkinson
Journal: New England Journal of Medicine (2009)

A 16-year-old girl with juvenile dermatomyositis reported having had bleeding gums that had not responded to traditional dental treatment. Close examination of the mouth revealed markedly dilated capillaries in the attached gingiva, with bushy loop formations that spread over the lower teeth.
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans
Authors: Kunio Kitamura, Masako Yanazawa, Noriyuki Sugiyama, Hirohito Miura, Akiko Iizuka-Kogo, Masatomo Kusaka, Kayo Omichi, Rika Suzuki, Yuko Kato-Fukui, Kyoko Kamiirisa, Mina Matsuo, Shin-ichi Kamijo, Megumi Kasahara, Hidefumi Yoshioka, Tsutomu Ogata, Takayuki Fukuda, Ikuko Kondo, Mitsuhiro Kato, William B. Dobyns, Minesuke Yokoyama, Ken-ichirou Morohashi
Journal: Nature Genetics (2002)
Prediction and preparation: Anticipatory role of the cerebellum in diverse neurobehavioral functions
Authors: Eric Courchesne
Journal: Behavioral and Brain Sciences (1997)

Braitenberg et al.'s view that the cerebellum contributes “mechanical efficiency” to multijoint sequences of movement is too narrow to account adequately for results from new anatomical, neurobehavioral, and neuroimaging studies. A broader view is that the cerebellum modulates attention, sensory, motor, and other neural systems in order to accomplish its prime function, which is to learn to predict and prepare for imminent information acquisition, analysis, or action.
Trace elements in cerebrospinal fluid in motor neurone disease.
Authors: J D Mitchell, I A Harris, B W East, B Pentland
Journal: BMJ (1984)

Concentrations of sodium, chlorine, potassium, chromium, iron, cobalt, zinc, rubidium, silver, caesium, and selenium in cerebrospinal fluid from 14 control subjects and 20 patients with motor neurone disease were measured by in vitro neutron activation analysis. No statistically significant correlation was found between the concentrations of any two elements other than sodium and chlorine in either the patient or control group (r = 0.9905; p less than 0.001). The mean cobalt concentration was significantly lower in the patients (p = 0.0015). No other statistically significant difference was shown. The relevance of this finding was examined in relation to current concepts of the pathogenesis of motor neurone disease and the role of cobalt in cellular metabolism.
The Digital Artery Lesion of Rheumatoid Arthritis: AN IMMUNOFLUORESCENT STUDY
Authors: W. Douglas
Journal: Annals of the Rheumatic Diseases (1965)

Obliterative endarteritis affecting digital and visceral vessels in rheumatoid arthritis was first described in detail by Bywaters (1957), although Kestler (1949) andCruickshank (1954) had previously referred to a subacute endarteritis in this disease.The relationship between this form of arterial lesion and the necrotizing arteritis sometimes occurring in rheumatoid disease (Ball, 1954) remains unexplained, although it has been noted by Bywaters (1957) and by Sokoloff and Bunim (1957) that both arterial lesions may occur in the same individual.Histologically, the obliterative endarteritis of digital vessels in patients with rheumatoid arthritis is characterized by a more or less concentric increase of intimal fibrous tissue, largely free of inflammatory cells.The internal elastic lamina usually remains intact, although when intimal thickening is marked there may be splitting of elastic fibres and thrombosis with resultant occlusion of the artery.Clinically, the condition is often asymptomatic, although cold digits, Raynaud's phenomenon, and ischaemic lesions in the form of nail-fold and finger- pulp thrombosis may be encountered.Brachial angiography has been used to study the digital arteries of rheumatoid patients by Scott, Hourihane, Doyle, Steiner, Laws, Dixon, and Bywaters (1961) and by Laws, Lillie, and Scott (1963).These workers found that the digital vessels frequently showed narrowing or complete occlusion.They also pointed out that nearly all patients showing these lesions had positive serum titres for rheumatoid factor.In the present study immunofluorescent methods have been used to determine whether rheumatoid factor is present within the intimal lesion of digital arteries from patients with rheumatoid arthritis.
THE ANTISTREPTOCOCCAL PROPERTY OF MILK
Authors: Armine T. Wilson, Herman Rosenblum
Journal: The Journal of Experimental Medicine (1952)

Lactenin is reversibly inactivated by the exclusion of atmospheric oxygen. It is also inactivated by the sulfur-containing reducing agents cysteine, glutathione, thioglycollic acid, and BAL. Group A streptococci which have been acted upon by lactenin have been killed, and not merely prevented from multiplying, since they cannot be revived by inactivating lactenin through the addition of a reducing agent. Thiamine in great excess inactivates lactenin. The mechanism by which it accomplishes this has not been discovered, but it suggests that the mode of action of lactenin may be to deny thiamine to the lactenin-sensitive cell. Lactenin sensitivity is not, however, related to a requirement for exogenous thiamine, nor does lactenin appear to function by binding environmental thiamine in a form unavailable to the sensitive cell.
Abstract 4878: Application of a novel nano-immunoassay platform to assess changes in cIAP1 in response to the SMAC-mimetic, LCL161
Authors: Lakshmi Yeleswarapu, Shanthy Nuti, Armin Graber, Humphrey Gardner, Carl Barrett, Thiruvamoor Ramkumar
Journal: Cancer Research (2011)

Abstract Introduction: cIAP1 is member of a class of inhibitor of apoptosis proteins (IAP) that function in a regulatory role to prevent unintended cell death by apoptosis. LCL161 is a small molecule antagonist of IAPs that reverses cIAP1 inhibition of caspases, causing apoptosis. The present study explores the use of the Nano Pro 1000, a novel proteomic platform to measure the changes in cellular cIAP1 in response to treatment with LCL161. Methods: SKOV3 cells, peripheral blood mononuclear cells (PBMC) and hair follicles collected from healthy donors were treated with LCL161 for different times and subjected to capillary iso-electric focusing. Immunodetection was performed using antibodies directed against cIAP1 and the signal was quantified using HRP-labeled chemiluminescence reagents. Data from the Nano Pro were compared to results from western blots run in parallel. Results: We report that results from the nano-immunoassay are reproducible and correlate well with the western blotting data. Modulation in the cellular levels of cIAP1 in response to LCL161 treatment could be captured in samples containing as little as 1 ng of total protein. Similar modulation of cIAP1 was seen upon exposure to LCL161 in the studied test matrices. Conclusions: This novel proteomic tool is more sensitive, specific and quantitative compared to the currently available option of western blotting assays which are labor intensive, and have a relatively low throughput. Measurable signals corresponding to cIAP1 levels can be detected in matrices like PBMCs and hair follicles. The modulation of cIAP1 levels in these matrices mirror that seen in SKOV3 cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4878. doi:10.1158/1538-7445.AM2011-4878
Sleep Disturbance and Onset of Type 2 Diabetes
Authors: Norito Kawakami, Naoyoshi Takatsuka, Hiroyuki Shimizu
Journal: Diabetes Care (2004)

Sleep disturbance, which is often observed among patients with diabetes (1), is possibly caused by impaired glucose metabolism or physical and psychological discomfort due to the disorder. In addition, a recent prospective study of women has indicated an interesting association between sleep patterns and later-onset type 2 diabetes, with a greater incidence among both short-term ( 8 h) sleepers (2). Disturbance in sleep quality may also affect the later onset of overt diagnosis of type 2 diabetes. We investigated the association between sleep disturbance and the subsequent onset of type 2 diabetes in a group of Japanese …
Immune responses after immunization with plasmid DNA encoding Bet v 1, the major allergen of birch pollen
Authors: Arnulf Hartl, Jan Kiesslich, Richard Weiss, Andrea Bernhaupt, Sven Mostböck, Sandra Scheiblhofer, Christof Ebner, Fátima Ferreira, Josef Thalhamer
Journal: Journal of Allergy and Clinical Immunology (1999)
Effect of deoxycholate on immunoglobulin G concentration in bile: Studies in humans and pigs*1
Authors: Juan Ramon Sanabria, Aravinda Upadhya, Brendan Mullen, P. Robert C Harvey, Steven M. Strasberg
Journal: Hepatology (1995)

Because an increase in biliary deoxycholate levels seems to be a risk factor for cholesterol gallstone formation, we determined the relationship between deoxycholate levels and levels of the pronucleating protein, immunoglobulin G (Ig) in human gallbladder bile. Patients with cholesterol gallstones had a higher concentration of biliary IgG compared with a pigmented stone group and control patients. This was associated with the simultaneous presence of two conditions in the cholesterol stone group, supersaturated bile and a high deoxycholate/cholate ratio. The other patient groups met only one of the two conditions. Next, animal studies were performed to determine if model biles mimicking the two conditions could affect IgG secretion by the gallbladder. Gallbladders were exposed in vivo and then in an Ussing chamber to model biles. The voltage clamp technique was used to monitor functional integrity of the preparation. Three different model biles were tested: (1) taurodeoxycholate (TDC), 80%; taurocholate (TC), 20%; and cholesterol saturation index (CSI), 1.2; (2) TDC, 20%; TC, 80%; and CSI, 1.2; and (3) TDC, 80%; TC, 20%; and CSI, 0.6. IgG concentrations became significantly higher in group 1 than in the other two groups. The concentration of mucous glycoprotein was also significantly greater in group 1 when compared with group 2. Plasma cells were increased in number in mucosal and submucosal layers in group 1. We conclude that cholesterol supersaturated model bile with high content of TDC induces gallbladder epithelial alterations, which increase the luminal concentration of IgG and mucous glycoprotein.
100,000 HIPs Could Never Be Wrong
Authors: G. G. Liddle
Journal: JAMA (1966)

To the Editor:—  The HIPs of New York are Health Insurance Planees, and exactly 100,000 or approximately 110,000 of them have been put to work to bring in some statistics. The variation in figures is yours ( JAMA  197 , Sept 26, 1966, adv p 46).  The real question is that of the statistical importance. Hundreds of complaints arise from publications in which the authors see significance in observations of too small samples. The HIP study is going to beat the chi-squares round, and push the P -is-less-than 0.01 back to P   This troubles me, because there must be a limit to statistical significances. Mathematically, is P  P
An unusual case of quadriparesis
Authors: G. Ahmad, J. Vassallo, J. Naqvi, N. Khanna
Journal: BMJ (2013)

A 48 year old man presented with a four day history of lethargy, dizziness, and an unsteady gait with recurrent falls, on a background of chronic alcohol misuse. The patient was taking desmopressin for nocturnal enuresis and bendroflumethiazide for hypertension, which were both stopped on admission.

On physical examination he appeared clinically euvolaemic and he had no focal neurological deficit. Vital signs were within normal limits. Serum biochemistry showed sodium of 110 mmol/L (normal range 137-145; 1 mmol/L=1mEq/L) and potassium of 2.6 mmol/L (normal range 3.5-5.5 mmol/L). A computed tomogram of the brain that was performed to rule out traumatic brain injury was unremarkable.

Fluids were subsequently restricted and he was started on parenteral thiamine, oral chlordiazepoxide, and intravenous 0.9% sodium chloride with potassium supplementation. Twenty four hours later, serum sodium was 119 mmol/L and serum potassium was 3.3 mmol/L. Serum sodium eventually reached 130 mmol/L on day 4.

Seven days after admission he developed delirium and on examination had bilateral pyramidal weakness, more pronounced on the right. Reflexes were generally brisk, with bilateral extensor plantar responses. He also developed mild dysarthria but there was no dysphagia.

A repeat computed tomogram of the brain was normal. Magnetic resonance imaging of the brain was subsequently performed to obtain better images of the brainstem and posterior fossa (fig 1⇓).



Fig 1 Axial T2 weighted magnetic resonance imaging of the head





### 1 What does the magnetic resonance imaging scan show and what is the most likely diagnosis?

#### Short answer

A hyperintense triangular lesion in the central pons with peripheral sparing. In the clinical context of spastic quadriparesis, this is consistent with central pontine …
Down-regulation of interferon-γ signaling by gene transfer of Stat1 mutant in mesangial cells
Authors: Minoru Sakatsume, Ichiei Narita, Hajime Yamazaki, Akihiko Saito, Yoichi Nakagawa, Hideyuki Kuriyama, Ryozo Kuwano, Fumitake Gejyo, Masaaki Arakawa
Journal: Kidney International (2000)
Treatment of pain in adults with sickle cell disease
Authors: Samir K. Ballas
Journal: American Journal of Hematology (1990)

Abstract The treatment of an adult patient with sickle cell disease whose clinical course is characterized by frequent painful crises creates a number of logistic problems in a tertiary care city hospital. Because such patients usually have no objective signs of painful crises, they are often considered to be malingerers and drug abusers. This paper reviews this controversial issue and presents one attempt at its resolution.
Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study
Authors: Graziano Onder, Brenda WJH Penninx, Rajesh Balkrishnan, Linda P Fried, Paulo HM Chaves, Jeff Williamson, Christy Carter, Mauro Di Bari, Jack M Guralnik, Marco Pahor
Journal: The Lancet (2002)
Recent Trends in Medical Education
Authors: George T. Harrell
Journal: JAMA (1977)

The Macy Foundation over the years has held a number of conferences on medical education. This book briefly summarizes a survey taken to examine changes five years after a conference on curriculum. The main part consists of papers and discussion by educators from Canada and the United States at a new conference on trends and developments. Articles are grouped on the topics of students, curriculum in general, specific subjects, examinations, regional programs, and a forecast for 1985. Students now are seen as more serious, of better quality, and more goal oriented. Curricular changes have introduced some new material and dropped some. A trend away from three-year and accelerated programs was detected. Early introduction of clinical material, courses on family practice, and use of self- or independent study were noted. Schools are returning to letter or numerical grades rather than mere pass-fail. The increase in number of applications poses problems for
Epidermal naevus in Proteus syndrome showing loss of heterozygosity for an inherited <i>PTEN</i> mutation
Authors: A. Loffeld, N.J. McLellan, T. Cole, S.J. Payne, D. Fricker, C. Moss
Journal: British Journal of Dermatology (2006)

A 3‐year‐old boy with Proteus syndrome has a novel germline p.Y68D mutation of the PTEN gene inherited from his mother who has Cowden syndrome. In addition, DNA extracted from curettings of his widespread epidermal naevus shows loss of heterozygosity for this mutation. To our knowledge, this has not been described before.
Case of Disease of the Brain: Lesion of the Left Anterior Lobe of the Cerebrum; Haemorrhagic Effusion between the Membranes
Authors: R. H. Powell
Journal: BMJ (1845)

BRAIN. 341 dng to syncope, pulse fell.to 120; in eight hours, an increase of pain, pulse 140; after a small bleeding, a blister, antimony and purgatives, the symptoms then yielded.CASE xvi.-A rigor forty-eight hours after delivery, -heat and pain as usual; in two hours more, pulse 138, *hypogastriuin tumid and tender; pain severe, in paroxysms; tongue white and dry; third day of disease, relief; and a good recovery after a bleeding to thirty -ounces, and active purgatives on the first day, and leeches on the second.CASE xx.-A natural labour, the first child; five days after delivery, pain in the uterus like labour pains, pulse 86; in four hours, pain very acute, pulse 134; -in the next six hours, fluid stools, tenderness not abated, pulse 120; vomiting from medicine; in twenty two hours from the attack pulse 106, belly painful.2nd day, exhausted by purging; belly tender; relief for three days, then a second relapse; pulse 130, but pain and heat not in proportion; then recovery.Mr. Hey's cases in 1814.-Afifth child.Fortyeight hours from delivery, throbbing pain in the head and uterus, pulse 120.3rd day, less pain after purging.4tb, more headache, belly tender and tumid, pulse 140, costiveness.5th, worse after relief, pulse more.rapid, free stools.6th, pulse 150.The next three days better; the two following days, belly tumid, much prostration.12th day of disease, pain in head, a low typhoid state: afterwards recovery!Mr. Hey bled, when the disease had continued forty-eight hours; the belly very tumid, and the puilse 160! CASE -.-A sixth child, placenta forcibly extracted, and flooding, which required brandy; forty hours after