tbuckley/cabot-search huggingface dataset:
Exocrine pancreatic disorders in transsgenic mice expressing human keratin 8
Authors: M. Llanos Casanova, Ana Bravo, Angel Ramírez, Gabriela Morreale de Escobar, Felipe Were, Glenn Merlino, Miguel Vidal, José L. Jorcano
Journal: Journal of Clinical Investigation (1999)

Keratins K8 and K18 are the major components of the intermediate-filament cytoskeleton of simple epithelia. Increased levels of these keratins have been correlated with various tumor cell characteristics, including progression to malignancy, invasive behavior, and drug sensitivity, although a role for K8/K18 in tumorigenesis has not yet been demonstrated. To examine the function of these keratins, we generated mice expressing the human K8 (hk8) gene, which leads to a moderate keratin-content increase in their simple epithelia. These mice displayed progressive exocrine pancreas alterations, including dysplasia and loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine by adipose tissue, as well as increased cell proliferation and apoptosis. Histological changes were not observed in other simple epithelia, such as the liver. Electron microscopy showed that transgenic acinar cells have keratins organized in abundant filament bundles dispersed throughout the cytoplasm, in contrast to control acinar cells, which have scarce and apically concentrated filaments. The phenotype found was very similar to that reported for transgenic mice expressing a dominant-negative mutant TGF-β type II receptor (TGFβRII mice). We show that these TGFβRII mutant mice also have elevated K8/K18 levels. These results indicate that simple epithelial keratins play a relevant role in the regulation of exocrine pancreas homeostasis and support the idea that disruption of mechanisms that normally regulate keratin expression in vivo could be related to inflammatory and neoplastic pancreatic disorders.
On the Opening of the Abdomen from the Vagina and Vaginal Fixation of the Uterus
Authors: J. W. Taylor
Journal: BMJ (1896)

PRIOFESSOR MURDOCH CAME ERON urged the niecessity of ilnternal as well as extern1al exam1in1ation, in order isot oiiiy to coinfirm the opiniioni form-ied uponi abdominal palpationi, but to detect aniy ablL)normllity in tlie pelvis or otlher coniditionls wllicl miglht have a beariig uponi the labour.He agreed witlh Dr. Herman.wlho had ably set before tlle meetinig tlle ideas now generally accepted, both as to the causes anid prevenitioin of puerperal fever.lie urged the niecessity of isolatioln, and gave the hiistory of tlhree outbreaks of fever in a lyinig-in lhospital wlichl Were staniiped out by tlle early removal of the inifeeted cases.VIII.-T.MTORE MIADDEN, M.D., Obstetric Plhysician, Mater Miscricordim lIospital.DR. MORE MADDEN said: We must all adiiit that nio ques- tioin of greater importaniee could be discussed ini tlhis Section tlhani that wlhiel lhas beeni so ably initroduced by Dr. Herman, althouglh some of uis, includinig myself, mnay lnot be prepared to acquiesce in all hlis views tliereon, iior to adopt ill their entirety all tIme minutime of the antiseptic precautionis wlhiel lhe has advocated.That the chief danger of tlle lying-in <condition arises from tlle probability of our patients becoming ilnfected by the pathogeniic micro-organiisms by wlichl puer- peral septiememia is communicated seemis uinquestioinable, and that our primary duty in suclh cases is tlle exclusion as far as possible of these sourees of sepsis is, of course, equally obvious.As to tlle metlhods by wlhiel tllis object may be attained, there appears to me to be still room for ilnvestigatioil and discussioni.FromIi my owni experienice I am
Association of Maternal Report of Infant and Toddler Gastrointestinal Symptoms With Autism
Authors: Michaeline Bresnahan, Mady Hornig, Andrew F. Schultz, Nina Gunnes, Deborah Hirtz, Kari Kveim Lie, Per Magnus, Ted Reichborn-Kjennerud, Christine Roth, Synnve Schjølberg, Camilla Stoltenberg, Pål Surén, Ezra Susser, W. Ian Lipkin
Journal: JAMA Psychiatry (2015)

Gastrointestinal (GI) comorbidities are frequently described in association with autism spectrum disorder (ASD). However, the prevalence of GI disturbances and the age at which such problems first appear are unclear, and their specificity for ASD compared with other neurodevelopmental disorders is uncertain.To compare maternal report of GI symptoms during the first 3 years of life in children with ASD, developmental delay (DD), and typical development (TD).This large prospective cohort study consists of participants in the Norwegian Mother and Child Cohort Study. During a 10-year period (January 1, 1999, through December 31, 2008), women throughout Norway were recruited at the first prenatal ultrasonographic visit (approximately 18 weeks' gestation). The study enrolled 95,278 mothers, 75,248 fathers, and 114,516 children. Our analyses are based on MoBa data released through October 1, 2013, and NPR diagnoses registered through December 31, 2012, and include children born from January 1, 2002, through December 31, 2008, with completed age 18- and 36-month questionnaires.We defined 3 groups of children: children with ASD (n = 195), children with DD and delayed language and/or motor development (n = 4636), and children with TD (n = 40 ,95).The GI symptoms were based on maternal report of constipation, diarrhea, and food allergy/intolerance.Children with ASD were at significantly increased odds of maternally reported constipation (adjusted odds ratio [aOR], 2.7; 95% CI, 1.9-3.8; P < .001) and food allergy/intolerance (aOR, 1.7; 95% CI, 1.1-2.6; P = .01) in the 6- to 18-month-old age period and diarrhea (aOR, 2.3; 95% CI, 1.5-3.6; P < .001), constipation (aOR, 1.6; 95% CI, 1.2-2.3; P < .01), and food allergy/intolerance (aOR, 2.0; 95% CI, 1.3-3.1; P < .01) in the 18- to 36-month-old age period compared with children with TD. Similar results for these symptom categories were observed in comparisons with children with DD, but ORs were slightly lower. Mothers of children with ASD were significantly more likely to report 1 or more GI symptom in either the 6- to 18-month or the 18- to 36-month-old age period and more than twice as likely to report at least 1 GI symptom in both age periods compared with mothers of children with TD or DD.In this large prospective cohort, maternally reported GI symptoms are more common and more often persistent during the first 3 years of life in children with ASD than in children with TD or DD.
Abstract 4588: Tumor distribution of anti-neuropilin-1 is affected by antibody dose level in a tumor xenograft mouse model
Authors: Daniela Bumbaca, Charles A. Boswell, Eduardo E. Mundo, Yan Xin, Hong Xiang, Ruediger E. Port, Michelle G. Schweiger, Shannon L. Stainton, Anil Bagri, Frank P. Theil, Paul J. Fielder, Leslie A. Khawli, Ben Q. Shen
Journal: Cancer Research (2011)

Abstract Neuropilin-1 (NRP1) is a VEGF165 and semaphorin receptor widely expressed by vascular endothelial cells in normal tissues and on some tumor cells. Blocking NRP1 with human IgG1 against its b domain has been shown to inhibit tumor growth in several preclinical models. The objective of this study was to assess tumor distribution of anti-NRP1 at different dose levels with the aim of supporting the clinical development of this antibody. Nude mice bearing HM7 tumors were administered [111In]-DOTA labeled anti-NRP1 in the presence of increasing amounts of unlabeled anti-NRP1 via single IV injection. Following dosing, blood and tumors were collected at pre-selected time points. Tumor distribution was evaluated by measuring the radioactivity levels in the tumor and blood samples using a gamma counter. The mice that received only the radiolabeled antibody had relatively low plasma and tumor radioactivity levels at all time points. The plasma and tumor radioactivity levels for all other dose groups were higher than those of the group that received only radiolabeled antibody due to the saturation of the normal tissue sink previously identified. Comparing the tumor to blood radioactivity ratios demonstrated that the different dose groups maintained maximum exposure in the tumor for variable lengths of time, depending on the dose level. At 24 hours post-dose, all doses greater than the radiolabeled antibody alone were able to maintain maximum exposure. Conversely, at 48 hours post-dose, doses ≥ 10 mg/kg were able to maintain that level, while at 120 hours post-dose, only doses ≥ 20 mg/kg were able to maintain maximum exposure. Taken together, this suggests that tumor distribution is both dose and time dependent. This approach has been used to aid the clinical dose selection for anti-NRP1 and may be a valuable tool for the clinical development of other targeted therapies. 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 4588. doi:10.1158/1538-7445.AM2011-4588
The Hospice Movement: An Oncologist's Viewpoint
Authors: N. MacDonald
Journal: CA A Cancer Journal for Clinicians (1984)

In this broad survey, we have touched on the recent creation of special facilities for patients with advanced cancer and their relevance to the overall program of cancer control. Also discussed were a number of ethical dilemmas arising from our efforts to provide improved care for the social and emotional problems afflicting our patients. When all is said and done, however, all our efforts are designed to alleviate human suffering. There may not be such a large gap between basic cancer research, medical oncology, and the hospice movement as has sometimes been perceived.
Precision of measurements of right and left ventricular volume by cine computed tomography.
Authors: S J Reiter, J A Rumberger, A J Feiring, W Stanford, M L Marcus
Journal: Circulation (1986)

Precise determination of left and right ventricular stroke volumes is limited with conventional imaging techniques. We determined whether right and left ventricular stroke volumes could be precisely measured with cine computed tomography (CT). Cine CT enables simultaneous imaging of the right and left ventricles at an 8 mm slice thickness with a maximal scanning rate of 17 frames/sec (50 msec acquisition intervals). In eight dogs, true right ventricular and left ventricular stroke volumes were determined by dividing thermodilution cardiac output by heart rate and/or with the use of an aortic electromagnetic flow probe implanted over a long term. After at least 5 sec of suspended respiration, cine CT images were acquired during central venous injection of a nonionic contrast agent. Multiple perturbations in stroke volume were induced in each dog by the administration of dobutamine, sodium pentobarbital, or sodium nitroprusside or by coronary artery occlusion. Right and left ventricular stroke volumes were obtained by Simpson's reconstruction of end-diastolic and end-systolic short-axis tomograms from apex to base. The cine CT left ventricular stroke volume (range 11 to 45 ml) correlated highly with the true left ventricular stroke volume (r = .99, slope = 1.01, y intercept = -0.2 ml, SEE = 1.5 ml, n = 25). The cine CT right ventricular stroke volume (range 11 to 34 ml) also correlated highly with the true right ventricular stroke volume (r = .98, slope = 0.9, y intercept = 2.2 ml, SEE = 1.7 ml, n = 15). In 12 studies, the mean difference between nearly simultaneous right and left ventricular stroke volumes by cine CT was 1.1 ml (range 0.1 to 3.2 ml). Calculation of right and left ventricular stroke volumes from data from cine CT were highly reproducible. Intraobserver variability in measurements of right ventricular stroke volume (r = 1.0, slope = 0.99, y intercept = 0.19 ml) and left ventricular stroke volume (r = 1.0, slope = 1.02, y intercept = -0.21 ml) was minimal. Interobserver variability in measurements of right ventricular stroke volume (r = .98, slope = 0.90, y intercept = 1.66 ml) and left ventricular stroke volume (r = .99, slope = 0.97, y intercept = -0.02 ml) was likewise minimal. Thus, precise and highly reproducible measurements of right and left ventricular stroke volumes can be obtained with cine CT.
Care of the Infant With Prolonged Ventilator Dependency
Authors: Eduardo Bancalari
Journal: JAMA (1987)

The improved survival of critically ill infants has resulted in a rapid increase in the number of patients who require prolonged respiratory support. As a result of this, neonatal and pediatric intensive care units are frequently faced with the dilemma of having to allocate a portion of their limited resources to the care of infants who remain ventilator dependent for extended periods.  Despite the magnitude of this problem, it has seldom been addressed in the medical literature. This may reflect the frustration inherent in this situation for care givers who are accustomed to dealing with acute rather than chronic illnesses. The article from Schreiner and collaborators 1 in this issue ofThe Journaldescribes many facets of this problem and raises several medical, ethical, and social issues.  The first and most important question that needs to be considered is whether different treatment strategies for infants with acute respiratory failure can influence
Splenorenal Arterial Anastomosis in the Treatment of Stenosis of the Renal Artery
Authors: Charles W. Parton, Donald C. Nabseth
Journal: New England Journal of Medicine (1958)

HYPERTENSION associated with stenosis of the renal artery is well recognized. After Goldblatt's1 classic experiments in which arterial hypertension was induced in animals by partial occlusion of the renal artery there was great interest in the role that stenosis of the renal artery might have in man. In 1937 Butler2 reported 2 cases of unilateral pyelonephritis associated with hypertension in which the blood pressure returned to normal after nephrectomy. This was followed by an era of enthusiasm for nephrectomy in patients with unilateral renal disease in which it was hoped that the concomitant hypertension might be relieved. However, the percentage . . .
Of mice and men: Androgen dynamics in dominance and reproduction
Authors: Denys deCatanzaro, Emily Spironello
Journal: Behavioral and Brain Sciences (1998)

In the animal literature, the concept of dominance usually links status in intermale encounters with differential reproductive success. Mazur &amp; Booth effectively review the human literature correlating testosterone with intermale competition, but more profound questions relating this to male–female dynamics have yet to be addressed in research with humans.
IgG, IgA and IgE autoantibodies against the ectodomain of BP180 in patients with bullous and cicatricial pemphigoid and linear IgA bullous dermatosis
Authors: S. Christophoridis, L. Büdinger, L. Borradori, T. Hunziker, H.F. Merk, M. Hertl
Journal: British Journal of Dermatology (2000)

Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin diseases characterized by autoantibodies against components of the epidermal basement membrane. Like most patients with BP, a significant subgroup of patients with CP has circulating IgG specific for BP180, a transmembraneous protein of hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to the extracellular portion of BP180.We aimed to determine whether, in these diseases, autoantibody reactivity to BP180 is restricted to distinct immunoglobulin subtypes.Utilizing a baculovirus-encoded form of the ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n = 10) and normal human control sera (n = 10) were analysed by immunoblot for IgG, IgA and IgE reactivity against BP180.All of 10 BP sera displayed IgG, IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively, contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10 IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to BP180.The presence of IgG and IgA autoantibody responses to BP180 in patients with three clinically distinct autoimmune bullous diseases indicates that an autoimmune response to the same distinct adhesion protein may lead to different clinical manifestations. It is therefore conceivable that variable epitopes of BP180 are targeted by the different autoantibody isotypes, resulting in the distinct clinical pictures.
Abstract 1683: High throughput membrane proteomics for the discovery of oncology targets ideally suited for the development of antibody drug conjugates (ADCs)
Authors: Jonathan A. Terrett, Ludmila Bozhenok, Blake Belanger, Inigo Montes, Dee Aud, Jim Ackroyd, Amanda Anderson, Michael Trang, Martin Barnes, Harry Lamble, Xiaohong Yu, Christian Rohlff
Journal: Cancer Research (2011)

Abstract Antibody Drug Conjugates (ADCs) are showing tremendous promise for cancer patients as recently demonstrated by the dramatic responses reported in breast cancer and Hodgkin's Lymphoma clinical trials to the ADCs T-DM1 and SGN-35. We have developed proteomics methods to enrich for membrane proteins that are expressed preferentially in cancer cells over normal cells. Potential ADC targetable proteins are then validated using the proprietary OGAP database as well as conventional expression analysis tools. The proteomics processes have identified novel cancer specific proteins as well as cancer specific isoforms of known proteins. These targets are then combined with large panels of antibodies to discover potential therapeutics with properties desirable for the development of ADCs. Antibodies are selected which : a) preferentially bind to tumor cells over normal cells, b) have good specificity and affinity, c) show high prevalence in target cancer indications by IHC, d) internalize on antigen binding, e) bind to relevant tox species tissues as they bind to human tissues. Here we describe the proteomics processes and use of the OGAP database and demonstrate the development of candidate therapeutic antibodies with the potential to become ADCs, which are directed to novel targets and cancer specific isoforms. 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 1683. doi:10.1158/1538-7445.AM2011-1683
A NOTE ON THE VALIDITY OF WECHSLER-BELLEVUE SCATTER
Authors: GERALD R. PASCAL, JEAN B. ZEAMAN
Journal: American Journal of Psychiatry (1949)

It is concluded (1) that the index score as a measure of Wechsler-Bellevue scatter empirically derived for this study shows a significant difference between normals (not patients) and neurotics, and between neurotics and psychotics; (2) that an estimate of progressive seriousness of psychological disturbance based on psychiatric diagnosis is reflected in an increased index score for 2 separate hospital populations; and (3) that the index score is an estimate of level of adjustment as evidenced by its ability to discriminate significantly between inpatient neurotics and working outpatient neurotics.
Death during recovery from severe malnutrition and its possible relationship to sodium pump activity in the leucocyte.
Authors: J Patrick
Journal: BMJ (1977)

The leucocyte data on four malnourished children who died suddenly when high-energy feeding was started were retrospectively analysed. The pretreatment rate constant for sodium efflux in leucocytes was higher and the intracellular sodium concentration lower in this group than in 13 malnourished children who recovered uneventfully with feeding. Two other children with unusual leucocyte electrolyte values and sodium pump activity were identified and closely monitored when high-energy treatment was begun. They rapidly developed the syndrome of extracellular fluid overload but were successfully treated with diuretics and digoxin. Though the precise relation between the findings in the leucocytes and the development of this overload syndrome is not clear, the pretreatment leucocyte values are nevertheless valuable in predicting which malnourished children are at risk of sudden death when refeeding is started.
Abstract 292: Modulation of cyr61/ccn1 expression in human cell lines by the polyphenolic compound resveratrol
Authors: Ricardo Monzon, Jennifer Prokop
Journal: Cancer Research (2012)

Abstract Resveratrol is the active compound in red grape skin believed to contribute to the protective effects of red wine in heart disease and has been implicated in the modulation of certain cancers. The matricellular protein CCN1/Cyr61 is involved in the regulation of cellular activities that control growth, programmed cell death, cellular motility and cell adhesion. Interestingly, many of the regulatory pathways that affect CCN1/Cyr61 expression are also affected by resveratrol action. In order to examine the possible link between CCN1/Cyr61 action and resveratrol's effects, human cell lines were used to analyze resveratrol's effects on CCN1/Cyr61 expression and function. Increased levels of CCN1/Cyr61 expression were observed in cells treated with resveratrol alone or combined with the stimulatory agents phorbol ester and epidermal growth factor (EGF). Analysis of CCN1/Cyr61 protein expression and cellular functions also revealed modulatory effects of reseveratrol treatment, however the role of upstream regulatory pathways in mediating reseveratrol action has yet to be addressed. Nevetheless, these studies offer preliminary evidence for the regulation of CNN1/Cyr61 expression by a putative modulator of cellular processes involved in heart disease and cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 292. doi:1538-7445.AM2012-292
Pyoderma gangrenosum after cholecystectomy.
Authors: A J Carr, R C Percival, K Rogers, C T Harrington
Journal: BMJ (1986)

CommentIntravenous treatment was used in these patients to exclude problems of absorption from the gastrointestinal tract.The combination oftrimethoprim and sulphadimidine was preferred to co-trimoxazole to prevent further compromising renal functions.4Monitoring the serum concentrations of trimethoprim lessens the risk of nephrotoxicity, and using sulphadimidine avoids the danger of haemorrhagic crystalluria with sulphamethoxazole.5 Intravenous administration of co-trimoxazole also meais giving large volumes ofdiluent, which are contraindicated in this group of patients.Adding sulphadimidine or trimethoprim to the cyclosporin radioimmunoassay in vitro or adding serum from patients being treated with these drugs but not with cyclosporin A did not influence the results of this assay.Furthermore, two patients developed rejection episodes while their serum cyclosporin concentrations were unrecordable, so we were convinced that the effect was not artefactual.As the trimethoprim concentrations remained constant throughout intravenous and oral treatment we think it probable that sulphadimidine was responsible for the decrease in serum cyclosporin.These cases emphasise that serum cyclosporin A concentrations must be closely monitored when a patient receiving this immunosuppressant is given concomitant treatment with a sulphonamide.In addition, histological proof of the presence of P carinii pneumonia should be obtained before starting a treatment that may precipitate rejection.We thank Miss Sally Smyth for her secretarial help.Measurement of serum cyclosporin values