tbuckley/cabot-search huggingface dataset:
Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response
Authors: E Furrie
Journal: Gut (2003)

<b>Background and aims:</b> The mucosa in ulcerative colitis (UC) is replete with antibody producing plasma B cells and polymorphonuclear leucocytes (PMN). This combination of effector cells requires a crosslinking antigen to evoke an antibody driven PMN inflammatory response via their Fc receptors. The stimulus for activation is thought to be commensal bacteria colonising the gut mucosa. The aim of this investigation was to compare the principal culturable bacterial populations on the rectal mucosa of UC patients, and to determine whether specific antibodies towards these bacteria can activate infiltrating PMN through opsonisation. This would provide an explanation for this chronic inflammatory condition. <b>Methods:</b> Bacteria colonising rectal tissue were characterised using chemotaxonomic techniques. Systemic antibody responses were measured against total antigens and surface antigens of these organisms in UC and Crohn's disease (CD) patients, together with healthy controls. Antibody enhancement of the respiratory burst in PMN was also investigated, against a range of mucosal isolates. <b>Results:</b> Distinct differences were observed in some bacterial populations in UC biopsies, which were generally reflected in antibody responses towards these organisms. UC patients had higher IgG responses to surface antigens, primarily IgG1, whereas the response in CD was mainly IgG2. Antibodies from UC patients greatly enhanced the respiratory burst in PMN, in response to individual bacterial species. <b>Conclusions:</b> Changes in mucosal bacteria, and a switch from internal to surface antigen/antibody reactivity of a predominantly IgG1 type, leads to greater opsonisation of the respiratory burst in PMN, providing a mechanism for maintaining the inflammatory state in UC.
Functionally Defined White Matter Reveals Segregated Pathways in Human Ventral Temporal Cortex Associated with Category-Specific Processing
Authors: Jesse Gomez, Franco Pestilli, Nathan Witthoft, Golijeh Golarai, Alina Liberman, Sonia Poltoratski, Jennifer Yoon, Kalanit Grill-Spector
Journal: Neuron (2015)
The amino acid-induced alteration in renal hemodynamics is glucagon independent.
Authors: T M Nammour, P E Williams, K F Badr, N N Abumrad, H R Jacobson
Journal: Journal of the American Society of Nephrology (1991)

The amino acid-induced alteration in renal hemodynamics is glucagon independent. An oral protein load or i.v. administration of an amino acid solution results in an increase in glomerular filtration rate and renal plasma flow in both humans and animals. The change in renal hemodynamics has been attributed to the simultaneous induced rise in glucagon. Whether glucagon is necessary for the change in renal hemodynamics after an amino acid infusion was investigated. Two groups of dogs were used, and the experimental protocol was divided into four different periods (P1 through P4). Group I animals received an amino acid solution, and group II dogs received an equiosmolar solution of mannitol. In P1, the animals in both groups were hydrated with normal saline, whereas, in P2, the pancreatic clamp technique was used to fix the plasma glucagon levels. P2 served as a basal period in which measurements of glomerular filtration rate, renal plasma flow, and plasma glucagon were obtained. IN P3, group I animals received amino acid solution, and group II received mannitol and served as controls. In this period, an increase of 32 and 27% in glomerular filtration rate and renal plasma flow, respectively, in group I dogs was observed, whereas there were no significant changes in these parameters in group II. During this period, plasma glucagon remained still at basal level in both groups. In P4, an infusion of glucagon at a rate of 5 ng/kg/min was added to both groups. This maneuver resulted in a fourfold increase in plasma glucagon levels in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Cyclophosphamide Induces Differentiation of Th17 Cells in Cancer Patients
Authors: Sophie Viaud, Caroline Flament, Mustapha Zoubir, Patricia Pautier, Axel LeCesne, Vincent Ribrag, Jean-Charles Soria, Virginie Marty, Philippe Vielh, Caroline Robert, Nathalie Chaput, Laurence Zitvogel
Journal: Cancer Research (2010)

Low doses of the alkylating agent cyclophosphamide (CTX) mediate antiangiogenic and immunostimulatory effects, leading to potent tumoricidal activity in association with various immunotherapeutic strategies. Here, we show in rodents and cancer patients that CTX markedly promotes the differentiation of CD4(+) T helper 17 (Th17) cells that can be recovered in both blood and tumor beds. However, CTX does not convert regulatory T cells into Th17 cells. Because Th17 are potent inducers of tissue inflammation and autoimmunity, these results suggest impact on the clinical management of various types of malignancies treated with alkylating agents and a potential need to optimize CTX-based immunotherapy in patients.
National Resources for Continuing Medical Education
Authors: E. Grey Dimond
Journal: JAMA (1968)

During the past several months I have been on leave of absence as a visiting scholar at the National Library of Medicine. The time for contemplation was livened by the opportunity to observe first hand several federal health agencies, to study their relationship to each other, and to review the considerable health legislation of the 89th Congress. What I suggest here is from a private citizen viewpoint, tempered by persistent teaching and practice. I have no rigid belief in the inalterable soundness of what I advocate. Instead, my intent is to stimulate and, hopefully, by give and take, reason and reaction, see result certain missing ingredients in the present medical structure. <h3>Regional Medical Programs and National Medical Programs</h3> The excitement with launching of the Regional Medical Program (RMP) has obscured partially the substantial evidence that a nationwide, cohesive education program also has a role in the continuing education of 300,000
Dose-Response relationship of luteinizing hormone to luteinizing hormone—releasing hormone in man
Authors: Abba J. Kastin, Andrew V. Schally, Carlos Gual, A. Rees Midgley, M. Clinton Miller, Angela Cabeza
Journal: Journal of Clinical Investigation (1971)

In previous clinical studies with highly purified porcine luteinizing hormone-releasing hormone (LH-RH), administration of the somewhat arbitrarily chosen doses of 700-1500 mug resulted in increased serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The present study determined the minimum effective dose as well as the relationship of the response of serum LH and FSH to the dose of LH-RH administered. Three normal men received i.v. injections of 1.1-810 mug of LH-RH. A dose of 10 mug of LH-RH caused a statistically significant elevation in serum LH. 30 mug of LH-RH significantly increased serum FSH levels. A highly significant linear trend was observed in the log dose-response curve. The results indicate that both LH and FSH release occurs in man with doses of LH-RH much lower than previously used and that a linear log dose-response relationship can be obtained.
Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony.
Authors: C L Grines, T M Bashore, H Boudoulas, S Olson, P Shafer, C F Wooley
Journal: Circulation (1989)

Eighteen patients with isolated left bundle branch block (LBBB) were compared with 10 normal control subjects. Apexcardiograms, phonocardiograms, electrocardiograms, two-dimensional and dual M-mode echocardiograms, and radionuclide ventriculograms (RNV) were performed. There were no differences in the timing of right ventricular events between LBBB and normal subjects; however, striking delays in left ventricular systolic and diastolic events were apparent in the LBBB group. The delay was associated with shortening of left ventricular diastole and resultant increase in the ratio of right to left ventricular diastolic time in LBBB (1.2 +/- 0.08) compared with normal (1.0 +/- 0.06), p less than 0.0001. First heart sound (S1) amplitude, expressed as the ratio S1/S2, was decreased in LBBB compared with normal (0.67 +/- 0.2 compared with 1.34 +/- 0.25, p less than 0.01), in part due to wide separation of the valvular contributors to S1. The abnormal interventricular septal motion in LBBB corresponded to periods of asynchrony in contraction, ejection, end systole, and end diastole between right and left ventricles. Radionuclide ventriculograms revealed decreased regional ejection fraction of the septum in LBBB (40 +/- 16%) compared with 67 +/- 7% in normal subjects (p less than 0.001), while the apical and lateral regional ejection fractions were similar in the two groups. This loss of septal contribution resulted in a reduction in global ejection fraction in LBBB compared to normals (54 +/- 7% compared with 62 +/- 5%, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Increased plasma cholinesterase activity and succinylcholine resistance: a genetic variant.
Authors: H W Neitlich
Journal: Journal of Clinical Investigation (1966)

Quantitative variations of plasma cholinesterase activity (also called serum cholinesterase, pseudocholinesterase, nonspecific cholinesterase, or cho- linesterase II) are associated with several diseases.Slightly elevated levels have been observed in thy- rotoxicosis (1), schizophrenia (2), hypertension (3), acute emotional disorders, and after concus- sion (4).Markedly elevated levels, two to three times normal, occur with the nephrotic syndrome (5).Plasma cholinesterase activity is decreased in various disorders of the liver (6), in carcinoma (7), and after anticholinesterase drugs (8).Low plasma cholinesterase activity may signify the presence of a qualitatively different enzyme.Some surgical patients develop prolonged apnea after succinylcholine, a muscle relaxant normally hydrolyzed rapidly by cholinesterase; their plasma hydrolyzes cholinesterase substrates more slowly than usual (9).Several cholinesterase inhibitors such as dibucaine, physostigmine, and hexametho- nium are weak inhibitors of the atypical cholines- terase from these patients (10).Under standard- ized conditions, dibucaine inhibits the usual en- zyme more than 70%o, but the atypical enzyme is inhibited only 20%o (11).The per cent inhibition by dibucaine has become known as the dibucaine number.People with dibucaine numbers of about 20 are very sensitive to succinylcholine.Kalow and Staron determined the dibucaine numbers of 1,556 healthy and mentally ill subjects (12) and demonstrated that two allelic, codomi- nant, autosomal genes control the presence of the usual and atypical cholinesterase.Ninety-seven per cent of the population have dibucaine num- bers higher than 70 and are homozygous for the usual cholinesterase; 0.03%o have dibucaine num-
Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome
Authors: Vivian Chan, V. Wan Yin Chan, Ben Yip, C. S. Chim, T. K. Chan
Journal: American Journal of Hematology (1998)

A novel missense mutation (codon 351, GCT (Ala) → CCT (Pro)) of the FIX gene was characterised in a young female with mild hemophilia B. She is heterozygous for the FIX mutation inherited from her carrier mother. Analysis of the methyl-sensitive Hpa II sites at the 5′ end of the hypoxanthine phosphoribosyltransferase gene showed that skewed inactivation of the X chromosome carrying her normal FIX gene accounted for the hemophilia phenotype. Am. J. Hematol. 58:72–76, 1998. © 1998 Wiley-Liss, Inc.
Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal Cancer
Authors: Heather Hampel, Wendy L. Frankel, Edward Martin, Mark Arnold, Karamjit Khanduja, Philip Kuebler, Mark Clendenning, Kaisa Sotamaa, Thomas Prior, Judith A. Westman, Jenny Panescu, Dan Fix, Janet Lockman, Jennifer LaJeunesse, Ilene Comeras, Albert de la Chapelle
Journal: Journal of Clinical Oncology (2008)

Identifying individuals with Lynch syndrome (LS) is highly beneficial. However, it is unclear whether microsatellite instability (MSI) or immunohistochemistry (IHC) should be used as the screening test and whether screening should target all patients with colorectal cancer (CRC) or those in high-risk subgroups.MSI testing and IHC for the four mismatch repair proteins was performed on 500 tumors from unselected patients with CRC. If either MSI or IHC was abnormal, complete mutation analysis for the mismatch repair genes was performed.Among the 500 patients, 18 patients (3.6%) had LS. All 18 patients detected with LS (100%) had MSI-high tumors; 17 (94%) of 18 patients with LS were correctly predicted by IHC. Of the 18 probands, only eight patients (44%) were diagnosed at age younger than 50 years, and only 13 patients (72%) met the revised Bethesda guidelines. When these results were added to data on 1,066 previously studied patients, the entire study cohort (N = 1,566) showed an overall prevalence of 44 of 1,566 patients (2.8%; 95% CI, 2.1% to 3.8%) for LS. For each proband, on average, three additional family members carried MMR mutations.One of every 35 patients with CRC has LS, and each has at least three relatives with LS; all of whom can benefit from increased cancer surveillance. For screening, IHC is almost equally sensitive as MSI, but IHC is more readily available and helps to direct gene testing. Limiting tumor analysis to patients who fulfill Bethesda criteria would fail to identify 28% (or one in four) cases of LS.
P06.02 * ACTIVATION OF MULTIPLE GROWTH FACTOR SIGNALLING PATHWAYS IS FREQUENT IN MENINGIOMAS
Authors: C. O. Hanemann, D. Hilton, A. Shivane, L. Turner
Journal: Neuro-Oncology (2014)

Meningiomas are the most common type of primary intracranial tumour, which in a significant minority of cases are either histologically aggressive or surgically unresectable. Treatment of these latter tumours can be difficult, and currently there are very limited chemotherapeutic options available. We have investigated the expression of a number of growth factors, their receptors incl. activated forms and signalling pathways in 30 meningiomas and control tissue using immunohistochemical markers, and correlated expression with presumed NF2 gene status, by using fluorescent in situ hybridisation to look for chromosome 22q loss. The 8 meningiomas which showed evidence of loss from chromosome arm 22q by in situ hybridisation, had very similar patterns of expression to the remaining tumours. Our findings suggest that the majority of meningiomas show activation of multiple growth factor receptor pathways, irrespective of chromosome 22q loss, and may be susceptible to specific targeted therapeutic options directed against these pathways.
THE INFLUENCE OF POSTNATAL DEVELOPMENT ON DRUG-INDUCED HEPATIC PORPHYRIA AND THE SYNTHESIS OF CYTOCHROME P-450
Authors: Chull S. Song, Harold L. Moses, Alan S. Rosenthal, Nancy A. Gelb, Attallah Kappas
Journal: The Journal of Experimental Medicine (1971)

The mitochondrial enzyme delta-aminolevulinate synthetase (ALAS) controls the rate-limiting step in the synthesis of porphyrins and heme. An experimental form of hepatic porphyria can be readily elicited in laboratory animals, such as the rat, by drugs and foreign chemicals which are known to enhance the de novo formation of this enzyme in the liver. The present study shows that there is a striking refractoriness to the induction of ALAS during the perinatal period in the rat. Chemicals which have potent porphyria-inducing activity in adult animals have no significant inducing effect on hepatic ALAS in neonates. The ultrastructural changes which accompany the induction of ALAS by drugs and chemicals in adult liver also fail to take place in the livers of neonates. A progressive capacity for responding to the action of chemical inducers of hepatic ALAS does, however, develop in neonatal animals so that by approximately 5-6 wk of age experimental porphyria can be elicited as effectively in them as in adults. The reasons for the refractoriness of hepatic ALAS to induction in the perinatal period are not known; but the findings of this study make it clear that ALAS belongs to that increasingly large group of liver enzymes in mammals whose appearance, increase of activity, or inducibility is developmentally determined. The occurrence of developmental changes in the indicibility of ALAS in the liver of neonates also provided an opportunity to study the relationship of this enzyme activity to the drug-mediated induction of the hepatic hemoprotein cytochrome P-450. This inducible hemoprotein serves as the terminal oxygenase in the microsomal mixed-function oxidase system in the liver. The results of this study indicate that, in contrast to the refractoriness of ALAS to induction, significant drug-induced changes of hepatic P-450 content and of hemeprecursor incorporation into this cytochrome do take place in neonates. The synthesis of P-450 thus appears to be under a regulatory control different from that of ALAS in neonates, and the relation between ALAS activity and P-450 formation is not therefore a direct one.
Letter by Gasparini Regarding Article, “Syncope in High-Risk Cardiomyopathy Patients With Implantable Defibrillators: Frequency, Risk Factors, Mechanisms, and Association With Mortality: Results From the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Study”
Authors: Maurizio Gasparini
Journal: Circulation (2014)
Correlation between age and the secretions of melanocyte-stimulating cytokines in cultured keratinocytes and fibroblasts
Authors: M. Okazaki, K. Yoshimura, G. Uchida, K. Harii
Journal: British Journal of Dermatology (2005)

The majority of skin changes associated with ageing are caused by photoageing and reflect cumulative sun exposure. Although the actinic damage plays a major role in skin pigmentation, it is also important to examine the effects of chronological cellular ageing on the pigmentation. The chief cellular components of the skin other than melanocytes are keratinocytes and fibroblasts, and the influences of age-related changes in those cells on skin pigmentation have not been elucidated.To clarify the effects of cellular ageing of keratinocytes and fibroblasts on age-related skin pigmentation.Using ELISA analysis, we measured the level of melanogenic cytokines secreted by cultured keratinocytes and fibroblasts derived from skin of various chronological ages. We also compared the cytokine secretion by cultured keratinocytes between the second and fifth cultures.There was no correlation between age and hepatocyte growth factor (HGF), stem cell factor (SCF), and basic fibroblast growth factor (bFGF) secretion by fibroblasts. On the other hand, a significant positive correlation existed between age and interleukin ((IL)-1alpha secretion (R2=0.50, P=0.002), and a relatively weak correlation existed between age and endothelin-1 (ET-1) secretion (R2=0.17, P=0.051, not significant). The IL-1alpha secretion by keratinocytes was significantly increased in the fifth cultures compared with the second cultures (P<0.005).These findings suggest that IL-1alpha secretion increases as cells grow older, and the increased secretion of IL-1alpha by aged keratinocytes may stimulate HGF production in dermal fibroblasts paracrinely and ET-1 production in keratinocytes autocrinely, which stimulates melanocyte proliferation and induces an increase of tyrosinase activity in melanocytes. Because IL-1alpha is a primary mediator that responds to inflammation and injury, the transcription of genes involved in skin inflammation may be persistently induced in the aged skin. Thus the increased secretion of IL-1alpha by aged keratinocytes in the aged skin may play a role in the accentuated cutaneous pigmentation and other skin ageing.
Complement-Dependent Inflammation and Injury in a Murine Model of Brain Dead Donor Hearts
Authors: Carl Atkinson, Juan C. Varela, Stephen Tomlinson
Journal: Circulation Research (2009)

Rationale : Donor brain death (BD) is an unavoidable occurrence in heart transplantation and results in profound physiological derangements that render the heart more susceptible to ischemia/reperfusion injury in the recipient and likely has negative long-term consequences to allograft survival. Objective : We developed a novel mouse model of BD and investigated the role of complement in BD-induced myocardial inflammation and injury. Methods and Results : BD was induced by inflation of a balloon catheter in the cranial cavity. BD in wild-type mice resulted in a significant increase in serum concentrations of the complement activation product complement component (C)3a, and immunohistochemical analysis of heart sections demonstrated C3 deposition on the vascular endothelium and surrounding myocytes. Following induction of BD in complement (C3)-deficient mice, cardiac troponin levels, and histological evidence of injury were significantly reduced compared to wild-type mice. C3 deficiency was also associated with reduced myocardial leukocyte infiltration and reduced or absent expression of P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-α, and interleukin-1β. Conclusions : These data indicate an important role for complement in BD-induced inflammation and injury and suggest that a complement inhibitory strategy applied to the donor (in addition to the recipient) may provide graft protection.
Spontaneous increase of transforming growth factor beta production by bronchoalveolar mononuclear cells of patients with systemic autoimmune diseases affecting the lung.
Authors: Y Deguchi
Journal: Annals of the Rheumatic Diseases (1992)

The spontaneous increase in the transcription of the transforming growth factor beta (TGF beta) gene in bronchoalveolar mononuclear cells of patients with autoimmune diseases affecting the lung has been shown by northern blot assay and a nuclear run on transcription assay. Transcription of the TGF beta gene in bronchoalveolar mononuclear cells of patients with autoimmune diseases affecting the lung was increased 10 times compared with normal healthy subjects or patients with bronchial asthma as controls. This observation, confirmed by protein data, suggests that TGF beta, a potent mitogen for fibroblasts, may be produced in bronchoalveolar mononuclear cells during an active immune response in such patients and may be involved in autoimmune related changes of the pathophysiology of cytokine networks when the lung is affected, such as in lung fibrosis.