tbuckley/cabot-search huggingface dataset:
ANTAGONISTIC GROWTH PRINCIPLES OF SERUM AND THEIR RELATION TO OLD AGE
Authors: Alexis Carrel, Albert H. Ebeling
Journal: The Journal of Experimental Medicine (1923)

IT MAY BE CONCLUDED THAT, UNDER THE CONDITIONS OF THE EXPERIMENTS: 1. The inhibiting action on homologous fibroblasts of the heated serum of a young animal increases relatively more than that of an old animal. After it has been heated, the inhibiting action of the serum of the old animal is still greater than that of the young animal. 2. The CO(2) precipitate obtained from the serum of a young animal definitely increases the proliferative activity of homologous fibroblasts, while the CO(2) precipitate of the serum of an old animal has practically no activating power. After the removal of the CO(2) precipitate, the inhibiting action of the serum of young animals is increased, while that of old animals is not modified. 3. The increased inhibiting action of serum on homologous fibroblasts in old age is partly due to the disappearance of the growth-activating substances and to the enhanced activity of the growth-inhibiting principle.
A randomized phase II study of combination, alternating and sequential regimens of doxorubicin and docetaxel as first-line chemotherapy for women with metastatic breast cancer
Authors: S. Cresta, G. Grasselli, M. Mansutti, A. Martoni, G. Lelli, G. Capri, F. Buzzi, G. Robustelli Della Cuna, A. Jirillo, E. Terzoli, L. Frevola, E. Tarenzi, C. Sguotti, N. Azli, M. Murawsky, L. Gianni
Journal: Annals of Oncology (2004)

BackgroundThis randomized phase II study was conducted to evaluate the efficacy of doxorubicin and docetaxel (DOC) administered either as a combination, an alternating or a sequential regimen in women with metastatic breast cancer. Secondary objectives included overall response, time to progression, survival and safety.Patients and methodsPatients with breast cancer (n = 123) were randomized to receive doxorubicin and DOC either in combination (60 mg/m2 of each drug), or by alternated or sequential schedule (100 mg/m2 DOC and 75 mg/m2 doxorubicin) every 3 weeks for a maximum of eight cycles as first chemotherapy for stage IV disease. A second randomization allocated patients from each arm to receive prophylactic oral ciprofloxacin or no therapy to prevent febrile neutropenia.ResultsPatients received a median of eight cycles. In an intention-to-treat analysis, the overall response was 63%, 52% and 61% in the combination, alternating and sequential schedules, respectively. Corresponding rates of complete response were 15%, 14% and 11%. Grade 4 neutropenia was common in all arms (81%) and, together with febrile neutropenia, was significantly more frequent with the combination. Prophylaxis with ciprofloxacin did not reduce the incidence of febrile neutropenia or infection. Other frequent non-hematological adverse events included alopecia, nausea, vomiting, stomatitis and asthenia. Congestive heart failure only occurred in the combination arm (10%).ConclusionAll three schedules are feasible and endowed of good therapeutic activity. In view of the more pronounced toxicity and the risk of cardiac events because of the higher exposure to doxorubicin, the combination should be least favored when treating women with metastatic breast cancer. Prophylaxis with ciprofloxacin was ineffective and is not recommended.
Molecular characterization of major histocompatibility complex class II gene expression and demonstration of antigen-specific T cell response indicate a new phenotype in class II-deficient patients.
Authors: I Hauber, H Gulle, H M Wolf, M Maris, H Eggenbauer, M M Eibl
Journal: The Journal of Experimental Medicine (1995)

Major histocompatibility complex (MHC) class II deficiency is an inherited autosomal recessive combined immunodeficiency. The disease is known as bare lymphocyte syndrome (BLS). BLS is characterized by a lack of constitutive MHC class II expression on macrophages and B cells as well as a lack of induced MHC class II expression on cells other than professional antigen-presenting cells (APCs) due to the absence of mRNA and protein of the human leukocyte antigen (HLA) class II molecules, designated HLA-DR, -DQ, and -DP. The defect in gene expression is located at the transcriptional level and affects all class II genes simultaneously. Here we have analyzed transcription and protein expression of class II antigens in Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines and mononuclear cells (MNCs) of twin brothers. Whereas flow cytometric analysis failed to detect class II antigens on the cell surface of the patients' EBV-B cells and MNCs, examination of the genes coding for HLA-DR, -DQ, -DP, and the invariant chain (Ii) by reverse transcriptase-polymerase chain reaction amplification resulted in an unusual mRNA pattern in the B cell lines of the patients (HLA-DR alpha +, -DR beta, -DQ alpha +, -DQ beta -, -DP alpha -; -DP beta +, Ii+). In accordance with these findings no HLA-DR beta-specific protein was detected by immunoblotting, whereas low levels of HLA-DR alpha and normal levels of Ii were present. In contrast to EBV-B cells, the MNCs of both patients displayed a residual HLA-DR beta, -DQ beta, and -DP alpha mRNA signal. Furthermore, HLA-DR beta-specific protein was found in addition to HLA-DR alpha by immunoblotting of cell lysates, even though it was clearly decreased as compared with controls. Our results indicate that the defect in class II antigen expression is not necessarily present to the same extent in B cells and cells of other lineages. mRNA levels of HLA-DR beta were found to be enriched in adherent cells within the MNC fraction. Further investigations indicated that the MHC class II expressed is functional in antigen presentation, as the two boys' CD4+ T cells became activated and expressed interleukin-2R after stimulation of peripheral blood mononuclear cell cultures with recall antigen (tetanus toxoid). Furthermore, T cells tested in one of the two patients responded to both MHC class I and II allostimulation, and this response was inhibited by monoclonal antibodies of the respective specificity.(ABSTRACT TRUNCATED AT 400 WORDS)
Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype
Authors: Ritsuro Suzuki, Yoshitoyo Kagami, Kengo Takeuchi, Masahiro Kami, Masataka Okamoto, Ryo Ichinohasama, Naoyoshi Mori, Masaru Kojima, Tadashi Yoshino, Hirohiko Yamabe, Mami Shiota, Shigeo Mori, Michinori Ogura, Nobuyuki Hamajima, Masao Seto, Taizan Suchi, Yasuo Morishima, Shigeo Nakamura
Journal: Blood (2000)
Progression of Renal Disease in Henoch-Schönlein Purpura After Influenza Vaccination
Authors: Joseph A. Amato
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The article by Herron et al (242:53, 1979) reports convincingly the safety and efficacy of influenza vaccination in patients with various immunologically mediated diseases. Since there are no major complications of recent influenza vaccination on record, we want to report our experience with a patient with Henoch-Schönlein purpura, whose mild renal disease progressed irreversibly after influenza vaccination. <h3>Report of a Case.—</h3> A 23-year-old man with a ten-year history of Henoch-Schönlein purpura was hospitalized in November 1976, three weeks after vaccination with the whole bivalent influenza virus vaccine (A/NJ and A/Vict). The symptoms included fever, abdominal colics, gross hematuria, joint pains, and skin purpura. The blood pressure reading was 160/100 mm Hg. Stools were positive for blood, and the urine contained blood and RBC casts. The serum protein level was 4 g/24 hr. The level of serum BUN was 43 mg/dL; creatinine, 3.3 mg/dL; and creatinine clearance, 36
Epidermolysis bullosa acquisita with ultraviolet radiationsensitivity
Authors: U. Jappe, D. Zillikens, B. Bonnekoh, H. Gollnick
Journal: British Journal of Dermatology (2000)

Abstract A 37-year-old male patient developed a bullous eruption and erythematous plaques mainly in exposed areas following prolonged sun exposure. In addition, blisters were noted on oral and nasal mucous membranes. Histopathological examination of a lesional skin biopsy revealed a subepidermal blister. Linear deposition of IgG and C3 at the epidermal basement membrane zone was revealed by direct immunofluorescence microscopy of a perilesional skin biopsy. Indirect immunofluorescence on 1 mol/L salt-split skin showed binding of autoantibodies to the dermal side of the split. Immunoblot analysis of dermal extracts demonstrated that the patient’s serum contained IgG antibodies against type VII collagen, whereas no reaction was seen with epidermal extracts or by enzyme-linked immunosorbent assay using a recombinant form of bullous pemphigoid 180. Standardized ultraviolet (UV) radiation provocation induced blistering with both UVA (13·5 J/cm2) and UVB (0·04 J/cm2) within 24 h clinically and histologically. External and systemic UV-protective medication and nine cycles of high dosage immunoglobulins given intravenously (1·2 g/kg body weight over 2–3 days every 4 weeks) resulted in the cessation of blister formation. To the best of our knowledge, this is the first report of a case of epidermolysis bullosa acquisita with sensitivity to UV.
Case of Strangulated Right Femoral Hernia: Operation on Fourth Day of Strangulation: Recovery
Authors: A. Fleischmann
Journal: BMJ (1859)

ORI0GNAL OOMM OATIONS.[BArmn MDICAL JotWrn below the Vessels, and brought out the point just bfore the aus As I cut rapidly upwards, Mr. Heathoote followed the kfe with his finger Pressure with them and his thumb above the groin, secund the vesls as eoon as they were divided and not one ounce of blood was lost at this stage of the oe Mr. Keats, who had charge of the limb, then su4dzly depressd the thigh.Two strokes of the Jinife over th capsuir ligament were made, and the head of the femur started out of te atabulum, at the ame time tearing through the roud ligament.Disaticulation was rapidly of- feeted, and the separation of the limb completed by making a long posterior flap.All hemorrhage from the posterior flap was contolled by Mr. Pidduck.Five vessels only required the application of ligatures, and there was but very slight oozing from the surface.As soon as that had ceased, the posterior Sap wes folded upwards on the groin.Three sutures were in- serted, some strips of adhesive plaister applied, and over all a wet compress.
Inconsistent Use of Diabetes Medications, Diabetes Complications, and Mortality in Older Mexican Americans Over a 7-Year Period
Authors: Yong-Fang Kuo, Mukaila A. Raji, Kyriakos S. Markides, Laura A. Ray, David V. Espino, James S. Goodwin
Journal: Diabetes Care (2003)

The aim of this study was to examine the relationship between inconsistency in use of diabetes drugs and risk of renal, eye, and circulation problems and death over a 7-year period in community-dwelling older Mexican Americans.Data are from the four waves of the Hispanic Established Population for the Epidemiologic Study of the Elderly. In-home interviewers assessed consistency in use of diabetes medications among 908 diabetic Mexican Americans, aged >or=65 years. Diabetes and complications were by self-report. Subjects with poor consistency in use of medication were those who, at any time during the 7-year follow-up, discontinued or inconsistently used their diabetes medications and those who had no diabetic medications at home despite self-report of taking medicine for diabetes.Thirty-six percent of our sample were inconsistent with diabetes medication usage. Older age and lack of supplemental health insurance were significantly associated with inconsistency of use of medication. In a multivariate logistic regression model, subjects with poor consistency in use of medication were more likely to report kidney problems (odds ratio [OR] 1.59; 95% CI 1.13-2.23; P = 0.008) at follow-up compared with those with good consistency, after controlling for age, sex, medication type, duration of diabetes, education, income, marital status, language of interview, insurance status, cognitive function, presence of depressive symptoms, activities of daily living, and instrumental activities of daily living. In Cox regression models, poor consistency with diabetic medication was also associated with increased all-cause mortality (hazard ratio [HR] 1.43; 95% CI 1.13-1.82; P = 0.003) and diabetes-related deaths (1.66; 1.20-2.30; P = 0.002) over a 7-year period after adjusting for relevant confounders.Inconsistent use of diabetic medication was associated with an increased risk of kidney problems and deaths over a 7-year period in older Mexican Americans.
Lack of association between <i>HLA-G</i> 14 bp insertion/deletion polymorphism and response to long-term therapy with methotrexate response in rheumatoid arthritis: Table 1
Authors: L K Stamp, J L O’Donnell, P T Chapman, M L Barclay, M A Kennedy, C M A Frampton, R L Roberts
Journal: Annals of the Rheumatic Diseases (2008)

Pharmacogenetic studies examining methotrexate (MTX) response/toxicity have focused on enzymes involved in MTX transport and folate metabolism.1 However, recently it has been reported that patients with rheumatoid arthritis (RA) with the HLA-G −/−14 bp genotype are more likely to respond to MTX.2 3 Human leukocyte antigen (HLA)-G molecules are non-classical major histocompatability complex (MHC) class I antigens that play a role in the immune system.4

We investigated whether an association exists between the HLA-G −/−14 bp polymorphism and response to MTX in a cross-sectional study of patients with RA. Of the 130 patients recruited, 75.4% were female, 81% were rheumatoid factor (RF) positive and 67% …
Energy Intake and Prostate Tumor Growth, Angiogenesis, and Vascular Endothelial Growth Factor Expression
Authors: P. Mukherjee, A. V. Sotnikov, H. J. Mangian, J.-R. Zhou, W. J. Visek, S. K. Clinton
Journal: JNCI Journal of the National Cancer Institute (1999)

A sedentary lifestyle coupled with excessive energy intake is speculated to be a factor associated with increased incidence of prostate cancer. We have investigated the effects of energy intake on prostate tumor growth in experimental animals.Two transplantable prostate tumor models, i.e., the androgen-dependent Dunning R3327-H adenocarcinoma in rats and the androgen-sensitive LNCaP human carcinoma in severe combined immunodeficient mice, were studied. R3327-H tumor growth and relevant tumor biomarkers (proliferation index, apoptosis [programmed cell death], microvessel density, and vascular endothelial growth factor [VEGF] expression) were compared in ad libitum fed control rats, ad libitum fed castrated rats, and groups restricted in energy intake by 20% or 40%. A second set of experiments involving both tumor models examined tumor growth in ad libitum fed rats or in animals whose energy intake was restricted by 30% using three different methods, i.e., total diet restriction, carbohydrate restriction, or lipid restriction. All P values are two-sided.R3327-H tumors were smaller in energy-restricted or castrated rats than in control rats (P<.001). Tumors from energy-restricted rats exhibited changes in tumor architecture characterized by increased stroma and more homogeneous and smaller glands. In castrated rats, the tumor proliferation index was reduced (P<.0001), whereas apoptosis was increased in both energy-restricted (P<.001) and castrated (P<.001) rats. Tumor microvessel density and VEGF expression were reduced by energy restriction and castration (P<.003 versus control). Restriction of energy intake by reduction of carbohydrate intake, lipid intake, or total diet produced a similar inhibition of growth of R3327-H or LNCaP tumors. These effects were associated with reduced circulating insulin-like growth factor-I.Our observations are consistent with the hypothesis that energy restriction reduces prostate tumor growth by inhibiting tumor angiogenesis. Furthermore, dietary fat concentration does not influence prostate tumor growth when energy intake is reduced.
Neuropsychiatric Observations in the Western Region of Nigeria
Authors: T. A. Lambo
Journal: BMJ (1956)

PREVENTION OF TUBERCULOSIS BDICALJOURNAL progress the individual must eventually be willing to act, without compulsion, for his own benefit.Tuberculin-testing, miniature radiography, B.C.G. vaccination, and antibiotics are the four cardinal points of the compass that must be our guide to the eradica- tion of tuberculosis, but the compass must be firmly based and binnacled by sound general public health measures.The importance of the primary infection and the lesion it produces can hardly be overestimated, for the initial reaction of the tissues to this invasion influences the subsequent course of the disease.It is therefore essential that future preventive measures should be directed, in the first instance, to discovering and treating the primary lesion whenever it occurs.To do this serial tuberculin-testing of children and establish- ing free static miniature radiography services in all large towns are advocated.Every effort must be made to prevent the spread of infection from persons with active disease who live in or enter countries where the incidence of infection is low.This is the major reason why tuberculosis has become an international problem.The more favoured nations must assist those in whose country the disease is still a major public health problem, not only because of the danger that lies at the door, but because the elimination of disease and relief of suffering are duties that the healthy must accept for the benefit of all mankind.
Stimulation of Toll-Like Receptor 2 in Human Platelets Induces a Thromboinflammatory Response Through Activation of Phosphoinositide 3-Kinase
Authors: Price Blair, Sybille Rex, Olga Vitseva, Lea Beaulieu, Kahraman Tanriverdi, Subrata Chakrabarti, Chie Hayashi, Caroline A. Genco, Mark Iafrati, Jane E. Freedman
Journal: Circulation Research (2008)

Cells of the innate immune system use Toll-like receptors (TLRs) to initiate the proinflammatory response to microbial infection. Recent studies have shown acute infections are associated with a transient increase in the risk of vascular thrombotic events. Although platelets play a central role in acute thrombosis and accumulating evidence demonstrates their role in inflammation and innate immunity, investigations into the expression and functionality of platelet TLRs have been limited. In the present study, we demonstrate that human platelets express TLR2, TLR1, and TLR6. Incubation of isolated platelets with Pam 3 CSK4, a synthetic TLR2/TLR1 agonist, directly induced platelet aggregation and adhesion to collagen. These functional responses were inhibited in TLR2-deficient mice and, in human platelets, by pretreatment with TLR2-blocking antibody. Stimulation of platelet TLR2 also increased P-selectin surface expression, activation of integrin α IIb β 3 , generation of reactive oxygen species, and, in human whole blood, formation of platelet–neutrophil heterotypic aggregates. TLR2 stimulation also activated the phosphoinositide 3-kinase (PI3-K)/Akt signaling pathway in platelets, and inhibition of PI3-K significantly reduced Pam 3 CSK4-induced platelet responses. In vivo challenge with live Porphyromonas gingivalis , a Gram-negative pathogenic bacterium that uses TLR2 for innate immune signaling, also induced significant formation of platelet–neutrophil aggregates in wild-type but not TLR2-deficient mice. Together, these data provide the first demonstration that human platelets express functional TLR2 capable of recognizing bacterial components and activating the platelet thrombotic and/or inflammatory pathways. This work substantiates the role of platelets in the immune and inflammatory response and suggests a mechanism by which bacteria could directly activate platelets.
Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment
Authors: Axel Grothey, Daniel Sargent, Richard M. Goldberg, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2004)

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.
Predictors of Delayed Gastric Emptying in Diabetes
Authors: Karen L. Jones, Antonietta Russo, Julie E. Stevens, Judith M. Wishart, Melanie K. Berry, Michael Horowitz
Journal: Diabetes Care (2001)

OBJECTIVE—To define the predictors of the rate of gastric emptying in patients with diabetes. RESEARCH DESIGN AND METHODS—A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes). RESULTS—The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 ± 3.2 vs. 50.2 ± 3.6%, P &amp;lt; 0.005) and liquid (retention at 100 min 22.7 ± 1.7 vs. 16.0 ± 1.8%, P &amp;lt; 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P &amp;lt; 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids. CONCLUSIONS—We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.
Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner
Authors: Irah L King, Anne Fortier, Michael Tighe, John Dibble, Gerald F M Watts, Natacha Veerapen, Ann M Haberman, Gurdyal S Besra, Markus Mohrs, Michael B Brenner, Elizabeth A Leadbetter
Journal: Nature Immunology (2011)