tbuckley/cabot-search huggingface dataset:
The Experimental Production of Arthritis: A Review
Authors: D. L. Gardner
Journal: Annals of the Rheumatic Diseases (1960)

Thecauseofrheumatoid arthritis remains unknown.Forsomeyearsithasseemedthatthe pathogenesis ofthedisease mightbemoreeasily understood ifa convenient animalreplica were available forlaboratory study. Tothis endmuch workonanimal arthritis andtheresultant considerable literature beartribute. Nevertheless, it mustreluctantly beadmitted that notoneofthese formsofanimal arthritis isstrictly analogous tothe humandisease inwhich there isconclusive evidence neither ofinfection, ofchronic physical orchemical irritation, ofendocrine disturbance nor,inspite of suggestive serological changes, ofcausal immunological disorder. Thereasons determining this apparent inability toreproduce thedisease inanimals shouldbe examined. Thatrheumatoid arthritis isa disease peculiar totheprimates ortoman isapossibility thathasnotbeenexcluded. Thevalue offurther attempts toproduce varieties ofarthritis insmall rodents mustbeseriously questioned. Considerationofthisproblem, andtheneedforpromising lines offuture inquiry haveledthereviewer togather together those methods whichhavepreviously been adopted forthelaboratory study ofarthritis. Previous surveys ofthesubject arelisted inTable I. Noattempt hasbeenmadetodivide themethods according tothepurpose oftheinvestigator, butfor convenience themethods havebeenclassified as infective, chemical, endocrine, immunological, and physical. Itisclear thatthepopularity oftheseexperimental methods isdetermined bytheparticular era inwhichtheworkisperformed, while theexpressed purpose ofthestudies reflects contemporary interest inindividual diseases. Inthesamewaytheanimals chosenforinvestigation areusually thosemost easily available, cheapest, andmostreadily maintained, rather thanthose whichwould ontheoretical TABLEI
The ultrastructure of fibromyomatous myometrium and its relationship to infertility
Authors: P. Richards
Journal: Human Reproduction Update (1998)

The aim of this study was to determine whether the ultrastructure of the non-neoplastic myometrial portion (host myometrium) of fibromyomatous uteri is normal or abnormal when compared to that of fibromyomata and normal myometria. Myometrial samples from 23 normal and 54 fibromyomatous uteri were examined at the ultrastructural level using standard electron microscopy techniques. Ultrastructural abnormalities of certain cellular organelles were noted in myocytes of fibromyomata but not in those of normal or host myometria. The sarcolemmal dense bands of host myometrial myocytes were of significantly greater length than those of normal myometria, but not significantly different to those of fibromyomata. Consequently, the numbers of caveolae in host myometria and fibromyomata are conceivably decreased in comparison to normal myometria. Host myometria can be, therefore, considered to be structurally abnormal. The specific structural abnormality noted may affect calcium metabolism in these tissues by causing a decrease in the cellular calcium extrusion mechanism and thus raising intracellular calcium concentrations. Such an abnormality may provide an answer, in terms of contraction abnormalities, for the unexplained infertility that occurs in a small percentage of symptomatic myomatous patients.
Predictive Value of Tumor Ki-67 Expression in Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer
Authors: Giuseppe Viale, Meredith M. Regan, Mauro G. Mastropasqua, Fausto Maffini, Eugenio Maiorano, Marco Colleoni, Karen N. Price, Rastko Golouh, Tiziana Perin, R. W. Brown, Anikó Kovács, Komala Pillay, Christian Öhlschlegel, Barry A. Gusterson, Monica Castiglione-Gertsch, Richard D. Gelber, Aron Goldhirsch, Alan S. Coates
Journal: JNCI Journal of the National Cancer Institute (2008)

Several small studies have reported that having a high percentage of breast tumor cells that express the proliferation antigen Ki-67 (ie, a high Ki-67 labeling index) predicts better response to neoadjuvant chemotherapy. However, the predictive value of a high Ki-67 labeling index for response to adjuvant chemotherapy is unclear. To investigate whether Ki-67 labeling index predicts response to adjuvant chemoendocrine therapy, we assessed Ki-67 expression in tumor tissue from 1924 (70%) of 2732 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. A high Ki-67 labeling index was associated with other factors that predict poor prognosis. Among the 1521 patients with endocrine-responsive tumors, a high Ki-67 labeling index was associated with worse disease-free survival but the Ki-67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone. Thus, Ki-67 labeling index was an independent prognostic factor but was not predictive of better response to adjuvant chemotherapy in these studies.
Neoadjuvant capecitabine and docetaxel (plus trastuzumab): an effective non-anthracycline-based chemotherapy regimen for patients with locally advanced breast cancer
Authors: H. Wildiers, P. Neven, M.R. Christiaens, P. Squifflet, F. Amant, C. Weltens, A. Smeets, E. van Limbergen, G. Debrock, V. Renard, L. Van Eenoo, W. Wynendaele, R. Paridaens
Journal: Annals of Oncology (2010)
Enzyme Markers in Acute Leukemias: Advances During the Last Decade&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hans Guenter Drexler, Gerhard Gaedicke, Jun Minowada
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Enzyme Markers in Acute Leukemias: Advances During the Last Decade Get access Hans Guenter Drexler, Hans Guenter Drexler 3Departments of Surgery and Pathology, Loyola University, Chicago, Ill. 60626, and Hines Veterans Administration Medical Center, Hines, Ill. 60141. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerhard Gaedicke, Gerhard Gaedicke 5Zentrum fuer Kinderheilkunde der Universitaet Ulm, Abteilung Kinderheilkunde II, Ulm, Federal Republic of Germany. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jun Minowada Jun Minowada 6 3Departments of Surgery and Pathology, Loyola University, Chicago, Ill. 60626, and Hines Veterans Administration Medical Center, Hines, Ill. 60141. 6Address reprint requests to Dr. Minowada, Edward J. Hines, Jr., Veterans Administration Hospital, Room 1A-333, 5th and Roosevelt Rd., Hines, Ill. 60141. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 72, Issue 6, June 1984, Pages 1283–1298, https://doi.org/10.1093/jnci/72.6.1283 Published: 01 June 1984 Article history Received: 25 August 1983 Accepted: 20 January 1984 Published: 01 June 1984
Microalbuminuria and the Risk for Early Progressive Renal Function Decline in Type 1 Diabetes
Authors: Bruce A. Perkins, Linda H. Ficociello, Betsy E. Ostrander, Kristen H. Silva, Janice Weinberg, James H. Warram, Andrzej S. Krolewski
Journal: Journal of the American Society of Nephrology (2007)

This study aimed to establish the time of initiation and the determinants of renal function decline in type 1 diabetes. Until now, such decline has been assumed to be a late-occurring event associated with proteinuria. A total of 267 patients with normoalbuminuria and 301 patients with microalbuminuria were followed for 8 to 12 yr. Linear trends (slopes) in GFR were estimated by serial measurement of serum cystatin C. Cases of early renal function decline were defined by loss in cystatin C GFR that exceeded -3.3%/yr, a threshold that corresponds to the 2.5th percentile of the distribution of GFR slopes in an independent nondiabetic normotensive population. Cases of early renal function decline occurred in 9% (mean slope -4.4; range -5.9 to -3.3%/yr) of the normoalbuminuria group and 31% (mean slope -7.1; range -23.8 to -3.3%/yr) of the microalbuminuria group (P < 0.001). Risk for early renal function decline depended on whether microalbuminuria regressed, remained stable, or progressed, rising from 16 to 32 and 68%, respectively (P < 0.001). In multivariate analysis, risk for decline was higher after age 35 yr or when glycosylated hemoglobin exceeded 9% but did not vary with diabetes duration, smoking, BP, or angiotensin-converting enzyme inhibitor treatment. Contrary to the existing paradigm of diabetic nephropathy, progressive renal function decline in type 1 diabetes is an early event that occurs in a large proportion of patients with microalbuminuria. Together with testing for microalbuminuria, clinical protocols using cystatin C to diagnose early renal function decline and track response to therapeutic interventions should be developed.
The Evolution and Adaptive Potential of Transcriptional Variation in Sticklebacks—Signatures of Selection and Widespread Heritability
Authors: Erica H. Leder, R.J. Scott McCairns, Tuomas Leinonen, José M. Cano, Heidi M. Viitaniemi, Mikko Nikinmaa, Craig R. Primmer, Juha Merilä
Journal: Molecular Biology and Evolution (2014)

Evidence implicating differential gene expression as a significant driver of evolutionary novelty continues to accumulate, but our understanding of the underlying sources of variation in expression, both environmental and genetic, is wanting. Heritability in particular may be underestimated when inferred from genetic mapping studies, the predominant "genetical genomics" approach to the study of expression variation. Such uncertainty represents a fundamental limitation to testing for adaptive evolution at the transcriptomic level. By studying the inheritance of expression levels in 10,495 genes (10,527 splice variants) in a threespine stickleback pedigree consisting of 563 individuals, half of which were subjected to a thermal treatment, we show that 74-98% of transcripts exhibit significant additive genetic variance. Dominance variance is also prevalent (41-99% of transcripts), and genetic sources of variation seem to play a more significant role in expression variance in the liver than a key environmental variable, temperature. Among-population comparisons suggest that the majority of differential expression in the liver is likely due to neutral divergence; however, we also show that signatures of directional selection may be more prevalent than those of stabilizing selection. This predominantly aligns with the neutral model of evolution for gene expression but also suggests that natural selection may still act on transcriptional variation in the wild. As genetic variation both within- and among-populations ultimately defines adaptive potential, these results indicate that broad adaptive potential may be found within the transcriptome.
Awareness of Breast Density and Its Impact on Breast Cancer Detection and Risk
Authors: Deborah J. Rhodes, Carmen Radecki Breitkopf, Jeanette Y. Ziegenfuss, Sarah M. Jenkins, Celine M. Vachon
Journal: Journal of Clinical Oncology (2015)

Purpose Legislation mandating disclosure of breast density (BD) information has passed in 21 states; however, actual awareness of BD and knowledge of its impact on breast cancer detection and risk are unknown. Methods We conducted a national cross-sectional survey administered in English and Spanish using a probability-based sample of screening-age women, with oversampling of Connecticut, the only state with BD legislation in effect for &gt; 1 year before the survey. Results Of 2,311 women surveyed, 65% responded. Overall, 58% of women had heard of BD, 49% knew that BD affects breast cancer detection, and 53% knew that BD affects cancer risk. After multivariable adjustment, increased BD awareness was associated with white non-Hispanic race/ethnicity (Hispanic v white non-Hispanic: odds ratio [OR], 0.23; P &lt; .001), household income (OR, 1.07 per category increase; P &lt; .001), education (OR, 1.19 per category increase; P &lt; .001), diagnostic evaluation after a mammogram (OR, 2.64; P &lt; .001), and postmenopausal hormone therapy (OR, 1.69; P = .002). Knowledge of the masking effect of BD was associated with higher household income (OR, 1.10; P &lt; .001), education (OR, 1.22; P = .01), prior breast biopsy (OR, 2.16; P &lt; .001), and residing in Connecticut (Connecticut v other states: OR, 3.82; P = .003). Connecticut residents were also more likely to have discussed their BD with a health care provider (67% v 43% for residents of other US states; P = .001). Conclusion Disparities in BD awareness and knowledge exist by race/ethnicity, education, and income. BD legislation seems to be effective in increasing knowledge of BD impact on breast cancer detection. These findings support continued and targeted efforts to improve BD awareness and knowledge among women eligible for screening mammography.
Platelet-induced neurogenic coronary contractions due to accumulation of the false neurotransmitter, 5-hydroxytryptamine.
Authors: R A Cohen
Journal: Journal of Clinical Investigation (1985)

The purpose of this study was to determine if 5-hydroxytryptamine released from aggregating platelets could be accumulated and released by canine coronary adrenergic nerves, and if the false neurotransmitter resulted in an abnormal response of the smooth muscle to nerve stimulation. Isometric tension was measured in rings of epicardial coronary suspended in organ chambers filled with physiological salt solution. The response to electrical stimulation or exogenously added norepinephrine was elicited after contraction with prostaglandin F2 alpha. Electrical stimulation and exogenous norepinephrine caused beta-adrenergic relaxation of control rings. However, after rings were exposed for 2 h to aggregating platelets or 5-hydroxytryptamine, electrical stimulation caused frequency-dependent contractions. These contractions were prevented by the serotonergic antagonists, cyproheptadine or ketanserin, or by the neuronal uptake inhibitor, cocaine. The relaxation caused by exogenously added norepinephrine was unchanged after exposure to platelets or 5-hydroxytryptamine, indicating that smooth muscle alpha- and beta-adrenergic responsiveness was unchanged. The electrically stimulated overflow of radiolabeled norepinephrine from superfused strips of coronary artery was not altered by prior exposure to 5-hydroxytryptamine, indicating that the effect of exposure on the response to electrical stimulation is primarily at smooth muscle serotonergic receptors. Canine coronary arteries accumulated and metabolized radiolabeled 5-hydroxytryptamine in vitro. The accumulation of 5-hydroxytryptamine was inhibited by cocaine or by adrenergic denervation with 6-hydroxydopamine but unaffected by removal of endothelium, indicating that the adrenergic nerves were the primary site of accumulation. Electrical stimulation of superfused strips of coronary artery preincubated with radiolabeled 5-hydroxytryptamine caused the release of the intact indoleamine; this was blocked by the neurotoxin, tetrodotoxin. These studies suggest that 5-hydroxytryptamine liberated from aggregating platelets may be accumulated by coronary adrenergic nerve endings. Upon its release from the nerves as a false transmitter, the amine can activate serotonergic receptors on the smooth muscle and reverse the action of the adrenergic nerves from dilator to constrictor.
Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat.
Authors: J H Oppenheimer, H L Schwartz, J T Lane, M P Thompson
Journal: Journal of Clinical Investigation (1991)

Metabolic balance studies were carried out to determine the interrelationships of thyroid hormone-induced lipogenesis, lipolysis, and energy balance in the free-living rat. Intraperitoneal doses of 15 micrograms triiodothyronine (T3)/100 g body wt per d caused an increase in caloric intake from 26.5 +/- 1.7 (mean +/- SEM) kcal/100 g per d to 38.1 +/- 1.5 kcal/100 g per d. Food intake, however, rose only after 4-6 d of treatment and was maximal by the 8th day. In contrast, total body basal oxygen consumption rose by 24 h and reached a maximum by 4 d. Since total urinary nitrogen excretion and hepatic phosphoenolpyruvate carboxykinase mRNA did not rise, gluconeogenesis from protein sources did not supply the needed substrate for the early increase in calorigenesis. Total body fat stores fell approximately 50% by the 6th day of treatment and could account for the entire increase in caloric expenditure during the initial period of T3 treatment. Total body lipogenesis increased within 1 d and reached a plateau 4-5 d after the start of T3 treatment. 15-19% of the increased caloric intake was channeled through lipogenesis, assuming glucose to be the sole substrate for lipogenesis. The metabolic cost of the increased lipogenesis, however, accounted for only 3-4% of the T3-induced increase in calorigenesis. These results suggest that fatty acids derived from adipose tissue are the primary source of substrate for thyroid hormone-induced calorigenesis and that the early increase in lipogenesis serves simply to maintain fat stores. Since the mRNAs coding for lipogenic enzymes rise many hours before oxygen consumption and lipolysis, these results suggest that T3 acts at least in part by an early coordinate induction of the genes responsible for these processes.
A single-tube allele specific-polymerase chain reaction to detect T315I resistant mutation in chronic myeloid leukemia patients
Authors: Wanwisa Wongboonma, Wanna Thongnoppakhun, Chirayu U Auewarakul
Journal: Journal of Hematology & Oncology (2011)

BCR-ABL kinase domain (KD) mutation is the major mechanism contributing to suboptimal response to tyrosine kinase inhibitors (TKI) in BCR-ABL-positive chronic myeloid leukemia (CML) patients. T315I mutation, as one of the most frequent KD mutations, has been shown to be strongly associated with TKI resistance and subsequent therapeutic failure. A simple and sensitive method is thus required to detect T315I mutation at the earliest stage.A single-tube allele specific-polymerase chain reaction (AS-PCR) method was developed to detect T315I mutation in a mixture of normal and mutant alleles of varying dilutions. Denaturing high performance liquid chromatography (DHPLC) and direct sequencing were performed as a comparison to AS-PCR.T315I mutant bands were observed in the mixtures containing as low as 0.5-1% of mutant alleles by AS-PCR. The detection sensitivity of DHPLC was around 1.5-3% dilution whereas sequencing analysis was unable to detect below 6.25% dilution.A single-tube AS-PCR is a rapid and sensitive screening method for T315I mutation. Detection of the most resistant leukemic clone in CML patients undergoing TKI therapy should be feasible with this simple and inexpensive method.
Pigmented viral warts: a clinical and histopathological study including human papillomavirus typing
Authors: None Egawa, None Honda, None Inaba, None Ono
Journal: British Journal of Dermatology (1998)

Although clinical, histological and viral correlations have recently been established among pigmented warts, homogeneous intracytoplasmic inclusion bodies and related types of human papillomavirus (HPV) (HPV 65, 4 and 60), the causes of the pigmentation remain unknown. In this study, comparative histological and histochemical analyses were performed with 53 pigmented (34 HPV 65-induced, 12 HPV 4-induced and seven HPV 60-induced) and 73 non-pigmented warts (27 HPV 2-induced, 23 HPV 1-induced, 12 HPV 63-induced, six unknown HPV-type induced and five HPV 60 induced) to clarify the causes of the pigmentation. Electron microscopy was also used to examine the pigmented warts. Many melanin blockade melanocytes were identified in all of the pigmented warts with Masson-Fontana staining and electron microscopy, and increased melanin in keratinocytes was also noted in 22 pigmented warts, suggesting that the dispersion of melanin granules in the dendrites of the melanin blockade melanocytes and the increased melanin granules in keratinocytes are the primary contributors to the pigmentation of the warts. The homogeneous intracytoplasmic inclusion bodies might also play a part in the darkening of the warts, as only the cases which had the inclusion bodies as well as the melanin blockade melanocytes were clinically pigmented. Although melanin blockade melanocytes were seen in a few cases of HPV 1- and HPV 2-induced warts in which the homogeneous inclusion bodies were not observed, the warts were not clinically pigmented. Melanin blockade melanocytes were not seen in any of the HPV 63-induced non-pigmented warts. In conclusion, the pigmented warts were associated with one of the related types of HPV (HPV 65, 4 and 60), and the pigmentation of the lesions is thus thought to be caused primarily by melanin blockade melanocytes. The homogeneous intracytoplasmic inclusion bodies might also play a part in the darkening of the lesions. This is the first report dealing with the pigmentary disorder associated with specific types of HPV.
Vaccination With Irradiated, Autologous Melanoma Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor by Adenoviral-Mediated Gene Transfer Augments Antitumor Immunity in Patients With Metastatic Melanoma
Authors: Robert Soiffer, F. Stephen Hodi, Frank Haluska, Ken Jung, Silke Gillessen, Samuel Singer, Kenneth Tanabe, Rosemary Duda, Steven Mentzer, Michael Jaklitsch, Raphael Bueno, Shirley Clift, Steve Hardy, Donna Neuberg, Richard Mulligan, Iain Webb, Martin Mihm, Glenn Dranoff
Journal: Journal of Clinical Oncology (2003)

Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) by retroviral-mediated gene transfer generates potent antitumor immunity in patients with metastatic melanoma. Further clinical development of this immunization scheme requires simplification of vaccine manufacture. We conducted a phase I clinical trial testing the biologic activity of vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer.Excised metastases were processed to single cells, transduced with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1 x 10(6), 4 x 10(6), or 1 x 10(7) tumor cells, depending on overall yield, and were injected intradermally and subcutaneously at weekly and biweekly intervals.Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 745 ng/106 cells/24 hours. Toxicities were restricted to grade 1 to 2 local skin reactions. Eight patients were withdrawn early because of rapid disease progression. Vaccination elicited dense dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates at injection sites in 19 of 26 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransduced tumor cells in 17 of 25 patients. Metastatic lesions that were resected after vaccination showed brisk or focal T-lymphocyte and plasma cell infiltrates with tumor necrosis in 10 of 16 patients. One complete, one partial, and one mixed response were noted. Ten patients (29%) are alive, with a minimum follow-up of 36 months; four of these patients have no evidence of disease.Vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma.
Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma
Authors: Chun-Yu Lo, Charalambos Michaeloudes, Pankaj K. Bhavsar, Chien-Da Huang, Chun-Hua Wang, Han-Pin Kuo, Kian Fan Chung
Journal: Journal of Allergy and Clinical Immunology (2014)