tbuckley/cabot-search huggingface dataset:
Nutritional therapy for high blood pressure. Final report of a four-year randomized controlled trial--the Hypertension Control Program
Authors: Rose Stamler, Jeremiah Stamler, Richard Grimm, Flora C. Gosch, Patricia Elmer, Alan Dyer, Reuben Berman, Joan Fishman, Nancy Van Heel, Jean Civinelli, Arline McDonald
Journal: JAMA (1987)

A four-year trial assessed whether less severe hypertensives could discontinue antihypertensive drug therapy, using nutritional means to control blood pressure. Randomization was to three groups: group 1—discontinue drug therapy and reduce overweight, excess salt, and alcohol; group 2—discontinue drug therapy, with no nutritional program; or group 3—continue drug therapy, with no nutritional program. In groups 1 and 2 patients resumed drug therapy if pressure rose to hypertensive levels. Loss of at least 4.5 kg (10+ lb) was maintained by 30% of group 1, with a group mean loss of 1.8 kg (4 lb); sodium intake fell 36% and modest alcohol intake reduction was reported. At four years, 39% in group 1 remained normotensive without drug therapy, compared with 5% in group 2. Study findings demonstrated that nutritional therapy may substitute for drugs in a sizable proportion of hypertensives or, if drugs are still needed, can lessen some unwanted biochemical effects of drug treatment. (<i>JAMA</i>1987;257:1484-1491)
Endocrine tumour in kidney affecting small bowel structure, motility, and absorptive function
Authors: M. H. Gleeson, S. R. Bloom, J. M. Polak, K. Henry, R. H. Dowling
Journal: Gut (1971)

A 44-year-old woman is described with an endocrine tumour arising in the kidney. There were associated abnormalities of small intestinal morphology, motility, and absorptive function. These abnormalities reversed on removal of the tumour. Detailed studies showed that the tumour contained, and was secreting, glucagon. It is postulated that the intestinal abnormalities may have resulted from glucagon itself or another, as yet unidentified, hormone.
Working memory, executive function, and general fluid intelligence are not the same
Authors: Richard P. Heitz, Thomas S. Redick, David Z. Hambrick, Michael J. Kane, Andrew R. A. Conway, Randall W. Engle
Journal: Behavioral and Brain Sciences (2006)

Blair equates the constructs of working memory (WM), executive function, and general fluid intelligence ( g F). We argue that there is good reason not to equate these constructs. We view WM and g F as separable but highly related, and suggest that the mechanism behind the relationship is controlled attention – an ability that is dependent on normal functioning of the prefrontal cortex.
The differential destructive and enhancing effects of anti-H-2K, H-2D, and anti-Ia antisera on murine skin allografts.
Authors: I F McKenzie, M M Henning
Journal: The Journal of Experimental Medicine (1978)

Nude (athymic) or anti-lymphocyte serum-treated mice have absent delayed graft rejection due to impaired T-cell responses. Nonetheless, these mice can reject skin grafts, acutely, when treated with anti-H-2 antibody and additional complement. Resolution of the components in the H-2 antisera, by either absorption or by selective production of antisera of restricted specificity has demonstrated that anti-H-2K or H-2D antiser are graft destructive, and as shown elsewhere, are nonenhancing. By contrast, anti-Ia sera are not capable of causing allograft destruction even when used in extremely high doses and were previously noted to be enhancing. The mechanism of such differential effects is not apparent, but the findings are clearly of importance to transplantation in man, where sera reacting specifically with B cells may also be enhancing and nondestructive.
Micrometastases and Isolated Tumor Cells in Breast Cancer Are Indeed Associated With Poorer Outcome
Authors: Paul J. van Diest, Maaike de Boer, Carolien H.M. van Deurzen, Vivianne C.G. Tjan-Heijnen
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: We read with interest the report by Hansen et al in a recent issue of Journal of Clinical Oncology concerning survival of patients with breast cancer according to size of their sentinel node metastases. The authors claim that patients with minimal metastatic tumor deposits, pN0(i ) or pN1mi, do not seem to have worse outcome compared with patients who are sentinel node negative. These results contradict our recently published results. We reported that isolated tumor cells and micrometastases were associated with an absolute reduction in 5-year disease-free survival of nearly 10%. In patients with isolated tumor cells or micrometastases who had received adjuvant systemic therapy, disease-free survival was improved compared with patients who did not receive systemic therapy. There could be several reasons for the discrepancy between results. Our study was much larger, with 819 pN0(i ) and 1032 pN1mi patients, compared with that by Hansel et al, with 84 pN0(i ) and 54 pN1mi patients. Furthermore, we considered final nodal status, whereas Hansen et al used sentinel node status only, though it is known that patients with isolated tumor cells and micrometastases may bear macrometastases in the nonsentinel nodes. Next, we revised and reclassified the pathology of all cases according to the sixth version of the AJCC Staging Manual. The authors claim that the study was prospective in design, but with enrollment from 1992 through 1999 and implementation of the sixth version of the staging manual in 2002, we have difficulty appreciating the data. The most relevant drawback of the study, also mentioned by the authors themselves, is the fact that 76.5% of patients received adjuvant systemic therapy, which may have clouded the impact of these metastases. We demonstrated that in patients with isolated tumor cells or micrometastases who were not treated with systemic therapy, outcome was reduced as compared with untreated node-negative patients, whereas in patients with isolated tumor cells or micrometastases who were treated with systemic therapy, outcome was reversed. Clearly, we would not have found a negative association with outcome if we had not analyzed outcome separately for patients who did versus who did not receive adjuvant systemic therapy. Inclusion of systemic therapy as a variable might have revealed this as important in the study by Hansen et al. Therefore, we feel that compared with our own study, the study by Hansen et al suffers from methodologic drawbacks, and we do not see any reason to doubt the negative prognostic impact of isolated tumor cells or micrometastases in breast cancer. Therefore, our more convincing results should be considered in future updates of the AJCC Staging Manual.
Troponin T isoform expression in humans. A comparison among normal and failing adult heart, fetal heart, and adult and fetal skeletal muscle.
Authors: P A Anderson, N N Malouf, A E Oakeley, E D Pagani, P D Allen
Journal: Circulation Research (1991)

The expression of troponin (Tn) T, a thin-filament regulatory protein, was examined in left ventricular myocardium from normal and from failing adult human hearts. The differences in isoform expression between normal and failing myocardium led us to examine the ontogenic expression of TnT in human striated muscle. Left ventricular samples were obtained from patients with severe heart failure undergoing cardiac transplantation and normal adult organ donors. Fetal muscle was obtained from aborted fetuses after 14-15 weeks of gestation, and adult skeletal muscle was obtained from surgical biopsies. Western blots of normal and failing adult heart proteins demonstrated that two isoforms, TnT1 and TnT2, are expressed in different amounts, with TnT2 being significantly greater in failing hearts (p less than 0.004). Western blots of two-dimensional gels of these proteins resolved two predominant spots of both TnT1 and TnT2 and several minor TnT species. Alkaline phosphatase treatment converted the two major spots of each isoform into the single more basic spots. A comparison of the ATPase activities and the TnT2 percentage of total TnT in individual failing and normal adult hearts demonstrated an inverse and negative relation (r = 0.7, p less than 0.02). In the fetal heart, four TnT isoforms were found, two of which had the same electrophoretic mobilities as the adult cardiac isoforms TnT1 and TnT2. Fetal skeletal muscle expressed two of the four fetal cardiac TnT isoforms, one of which comigrated with adult cardiac TnT1. These cardiac isoforms were expressed in low abundance in fetal skeletal muscle relative to seven fast skeletal muscle TnT isoforms. No cardiac isoforms were present in adult skeletal muscle. Because many etiologies caused heart failure in the transplant patients, we propose that the disease-associated increased expression of the TnT isoform TnT2 is an adaptation to the heart failure state and a partial recapitulation of the fetal expression of cardiac TnT isoforms.
Distal similarity, shape referents, subjective world, and redundancy
Authors: Hannes Eisler
Journal: Behavioral and Brain Sciences (1998)

The concept of distal similarity that plays a crucial role in Edelman's theory of representation is called into question in this commentary on theoretical as well as empirical grounds. A possible confusion between shape and (knowledge of) its referent, the problem of the subjective world, redundancy, and large individual differences in subjective space encountered in contrived universes are discussed.
FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study
Authors: Christophe Tournigand, Thierry André, Emmanuel Achille, Gérard Lledo, Michel Flesh, Dominique Mery-Mignard, Emmanuel Quinaux, Corinne Couteau, Marc Buyse, Gérard Ganem, Bruno Landi, Philippe Colin, Christophe Louvet, Aimery de Gramont
Journal: Journal of Clinical Oncology (2003)

In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B).
Human rheumatoid factor cross-idiotypes. IV. Studies on WA XId-positive IgM without rheumatoid factor activity provide evidence that the WA XId is not unique to rheumatoid factors and is distinct from the 17.109 and G6 XIds.
Authors: G B Knight, V Agnello, V Bonagura, J L Barnes, D J Panka, Q X Zhang
Journal: The Journal of Experimental Medicine (1993)

The WA cross-idiotype (XId) is the major XId among human monoclonal rheumatoid factors (mRF) and is almost always associated with the light (L) chain XId, 17.109, and the heavy (H) chain XId, G6. A cell line, 35G6, was cloned that bears the WA XId, but shows no reactivity with immunoglobulin G (IgG) and is negative for the 17.109 and G6 XIds. The 35G6 L chain appears to be derived from the same VKIII-JKI genes as most WA mRFs L chains. In contrast to the WA mRFs H chains in which VH1 genes are used, the 35G6 IgM expresses a VH3 gene. Sequence comparisons with other WA XId-positive mRF suggested several common structural features that may be related to the WA XId and differences that may relate to lack of IgG reactivity. Cells similar to 35G6 have previously been described in pokeweed mitogen-stimulated cell lines of peripheral blood lymphocytes from normal individuals and patients with rheumatoid arthritis and type II mixed cryoglobulinemia. These observations were confirmed, and in addition, it was shown that the majority of WA XId-positive cells in these cultures were negative for the 17.109 and G6 XIds. The presence of the WA XId in the absence of IgG reactivity suggests that the WA XId is more directly associated with an antigen specificity other than IgG, and its association with RF activity may be incidental. It is postulated that these WA XId-positive RF-negative antibodies may serve a physiologic role as natural antibodies to a pervasive pathogen, and that IgG reactivity is a consequence of somatic diversification accompanying proliferation of the WA XId-positive RF-negative cell.
Patient reported outcome measurement: learning to walk before we run
Authors: Alan Maynard, Karen Bloor
Journal: Journal of the Royal Society of Medicine (2010)

Although initiallyfocused on psychiatry, this system was alsoapplied to acute hospitals, in part because of theenthusiastic advocacy of Florence Nightingale.Emulating the 1845 legislation, she advocated themeasurement of outcomes in terms of whetherpatients were dead, relieved or unrelieved. Shedeclared:
Water Retention and Aquaporins in Heart Failure, Liver Disease and Pregnancy
Authors: Robert W Schrier, Melissa A Cadnapaphornchai, Mamiko Ohara
Journal: Journal of the Royal Society of Medicine (2001)

Water retention in excess of total body sodium frequently occurs in patients with cardiac failure or cirrhosis and in pregnancy. In fact, hyponatraemia signifies a poor prognosis in cardiac failure and cirrhosis1,2. The mechanism for this hyponatraemia, however, has not been well defined. In the era when the antidiuretic hormone (ADH) bioassay was performed in ethanol-anaesthetized rats, consistent alterations in ADH could not be demonstrated in hyponatraemic patients with cirrhosis or heart failure. Therefore it was suggested that intrarenal, non-ADH-dependent, mechanisms accounted for the water retention in these oedematous disorders.

Another dilemma in understanding fluid balance in cardiac failure, cirrhosis and pregnancy relates to defining the afferent signals that could stimulate AVP release with resultant water retention. Expanded plasma volumes have been reported in all three conditions. This finding is typically associated with increased water excretion rather than water retention; thus, signals other than increased plasma volume must contribute to the water retention.
Telomere Length in Peripheral Blood Lymphocytes Contributes to the Development of HPV-Associated Oropharyngeal Carcinoma
Authors: Yang Zhang, Erich M. Sturgis, Kristina R. Dahlstrom, Juyi Wen, Hongliang Liu, Qingyi Wei, Guojun Li, Zhensheng Liu
Journal: Cancer Research (2013)

Sexual transmission of human papillomavirus (HPV), particularly HPV16, has been associated with an increasing incidence of oropharyngeal squamous cell carcinoma (OPC). Telomere shortening results in chromosomal instability, subsequently leading to cancer development. Given that HPV16 can affect telomerase activity and telomere length, we conjectured that telomere length in peripheral blood lymphocytes (PBL) might affect the risk of HPV16-associated OPC and tumor HPV16 status in patients. Telomere length in PBLs and HPV16 serologic status were measured in peripheral blood samples in 188 patients with OPC, 137 patients with oral cavity cancer (OCC) and 335 controls of non-Hispanic Whites. Tumor HPV status was determined in 349 OPC cases. ORs and 95% confidence intervals were calculated in univariate and multivariable logistic regression models. Overall, as compared with the long telomere length, short telomere length was significantly associated with a moderately increased risk of OPC but not with increased risk of OCC. When we stratified the data by HPV16 serologic status, using long telomere length and HPV16 seronegativity as the reference group, we found that the risk associated with HPV16 seropositivity was higher among patients with OPC with short telomere length. Notably, such risk was particularly pronounced in never smokers, never drinkers, and those more than 50 years of age. Furthermore, short telomere length was also associated significantly with tumor HPV-positive OPC. Together, our findings suggest that telomere length in PBLs may be associated with higher risk of HPV16-associated OPC and tumor HPV16 status, particularly in certain patient subgroups. Larger studies are needed to validate these findings.
Interferon-Stimulated Genes: A Complex Web of Host Defenses
Authors: William M. Schneider, Meike Dittmann Chevillotte, Charles M. Rice
Journal: Annual Review of Immunology (2014)

Interferon-stimulated gene (ISG) products take on a number of diverse roles. Collectively, they are highly effective at resisting and controlling pathogens. In this review, we begin by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production. Next, we describe ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the JAK-STAT pathway. Several ISGs that directly inhibit virus infection are described with an emphasis on those that impact early and late stages of the virus life cycle. Finally, we describe ongoing efforts to identify and characterize antiviral ISGs, and we provide a forward-looking perspective on the ISG landscape.
Prospective Multicentric Randomized Study Comparing Periareolar and Peritumoral Injection of Radiotracer and Blue Dye for the Detection of Sentinel Lymph Node in Breast Sparing Procedures: FRANSENODE Trial
Authors: Jean-François Rodier, Michel Velten, Marc Wilt, Pierre Martel, Gwanaël Ferron, Véronique Vaini-Elies, Hervé Mignotte, Alain Brémond, Jean-Marc Classe, François Dravet, Thierry Routiot, Christine Tunon de Lara, Antoine Avril, Gérard Lorimier, Eric Fondrinier, Gilles Houvenaeghel, Sandrine Avigdor
Journal: Journal of Clinical Oncology (2007)

To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer.A prospective randomized multicentric study was initiated to compare the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients.The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001).This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.
Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope.
Authors: J T Safrit, C A Andrews, T Zhu, D D Ho, R A Koup
Journal: The Journal of Experimental Medicine (1994)

Virus-specific cytotoxic T lymphocytes (CTL) are involved in protective immunity to many virus infections. It has recently been shown that CTL are detectable early during primary infection with the primate lentiviruses, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. To better characterize the CTL response during acute HIV-1 infection, HIV-1-specific CTL clones were generated from two patients during symptomatic HIV-1 seroconversion. These CTL clones demonstrated specificity for env of HIV-1 and recognized sequences within gp41. Two human histocompatibility leukocyte antigen (HLA) A31-restricted clones from the same individual were found to have differing virus strain specificities. Both clones recognized the 11-amino acid peptide RLRDLLLIVTR from position 770-780 of gp41. A change from T to V at position 779 in this epitope abrogated lysis by one clone but not the other. A CTL clone from the other patient, restricted by a different class I HLA allele, recognized the nine-amino acid peptide HRLRDLLLI from position 769-777 of gp41. Of note, the peptide RLRDLLLIVTR has been shown by others to be presented to CTL by HLA-A3.1. Autologous virus sequences from seroconversion and up to 15 wk after presentation in these two patients were recognized by the CTL clones isolated during acute infection. None of the CTL clones recognized the MN strain of HIV-1, indicating the problems inherent in relying on a single virus strain in the development of a vaccine. These studies have identified an immunodominant and promiscuous area for the generation of CTL responses within gp41. This recognition of autologous virus sequences by the initial CTL response is consistent with the hypothesis that a single virus strain is transmitted to the seroconverter and that the CTL response is involved in the initial control of that virus. These studies indicate the importance of the CTL response to HIV-1 infection and have implications in the design of vaccines.
Obesity, Mammography Use and Accuracy, and Advanced Breast Cancer Risk
Authors: Karla Kerlikowske, Rod Walker, Diana L. Miglioretti, Arati Desai, Rachel Ballard-Barbash, Diana S. M. Buist
Journal: JNCI Journal of the National Cancer Institute (2008)

Being overweight or obese is associated with increased breast cancer risk and disease severity among postmenopausal women, but whether extent of mammography use and accuracy modify this association and further contribute to increases in disease severity at diagnosis among overweight and obese women is unclear. We prospectively collected data during 1996–2005 on 287 115 postmenopausal women not using hormone therapy (HT) who underwent 614 562 mammography examinations; 4446 women were diagnosed with breast cancer within 12 months of a mammography examination. We calculated rates per 1000 mammography examinations of large (>15 mm), advanced-stage (IIb, III, or IV), high-grade (3 or 4), estrogen receptor (ER)–positive and –negative, and screen-detected and non–screen-detected breast cancer across body mass index (BMI, kg/m 2 ) groups defined as normal (18.5–24.9), overweight (25.0–29.9), obese class I (30.0–34.9), and obese class II/III (≥35.0), adjusting for age, race/ethnicity, and mammography registry and use. All statistical tests were two-sided. Adjusted rates per 1000 mammography examinations of overall breast cancer increased across BMI groups (6.6 normal, 7.4 overweight, 7.9 obese I, 8.5 obese II/III; Ptrend < .001), as did rates of advanced disease, including large invasive (2.3 normal, 2.6 overweight, 2.9 obese I, 3.2 obese II/III; Ptrend < .001), advanced-stage (0.8 normal, 0.9 overweight, 1.3 obese I, 1.5 obese II/III; Ptrend < .001), and high nuclear grade (1.5 normal, 1.7 overweight, 1.7 obese I, 1.9 obese II/III; Ptrend = .10) tumors. Rates of ER-positive tumors increased across BMI groups ( Ptrend < .001); rates of ER-negative tumors did not. Rates of screen-detected cancers were higher among overweight and obese women than normal and underweight women, but rates of non–screen-detected (false-negative) cancers were similar. Rates of advanced breast cancer increased across BMI groups regardless of extent of mammography use. Patterns of mammography use and mammography accuracy are not the primary reasons for higher rates of advanced breast cancer among overweight and obese postmenopausal women not using HT; thus, biologic differences in breast tumor development and/or progression may be important.