tbuckley/cabot-search huggingface dataset:
The Health Needs of Older Hispanics
Authors: T. Franklin Williams
Journal: JAMA (1991)

<h3>To the Editor.—</h3> The January 9, 1991, issue ofThe Journal, which was devoted to the health care of Hispanic Americans, has particular significance for the nation's older Hispanics, the fastest growing age cohort in the United States. As of 1987, the US Census Bureau estimated that there were 906 000 Hispanic adults over the age of 65 years. The bureau projects that in less than 50 years, there will be 5.6 million older Hispanics—an astounding 600% increase. Older Hispanics suffer from greater poverty, live in worse conditions, and get less health care than the aging population as a whole. Indeed, older Hispanics are two to three times more likely to have long-term care needs relative to activities of daily living than non-Hispanic older persons. They also have the lowest health insurance coverage relative to any other age group in the United States.<sup>1</sup>That bodes poorly for enhancing current
AP-1 Proteins Mediate Hyperglycemia-Induced Activation of the Human TGF-β1 Promoter in Mesangial Cells
Authors: CORA WEIGERT, ULRICH SAUER, KATRIN BRODBECK, ANDREAS PFEIFFER, HANS U. HA[Combining Diaeresis]RING, ERWIN D. SCHLEICHER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Hyperglycemia-induced overproduction of the prosclerotic cytokine transforming growth factor-β1 (TGF-β1) has been implicated in the pathogenesis of diabetic nephropathy. Because high glucose and phorbol esters (PMA) increase TGF-β1 mRNA levels in mesangial cells, this study was designed to characterize these effects on the human TGF-β1 promoter activity. With the use of luciferase reporter gene constructs containing TGF-β1 5′-flanking sequence (from -453 to +11 bp) transfected into mesangial cells, it was found that 30 mM glucose induced a nearly twofold increase in TGF-β1 promoter activity after 24 h of incubation in human and porcine mesangial cells. Stimulation by PMA was more effective (2.3-fold). Mutagenesis in either one of the two or both activating protein-1 (AP-1) binding sites abolished the high glucose and the PMA effect. Furthermore, addition of the AP-1 inhibitor curcumin obliterated the glucose response. Corresponding experiments revealed that the transcription factor stimulating protein 1 was not involved in mediating the glucose effect. The high glucose-induced TGF-β1 promoter activation was also prevented by inhibitors of protein kinase C and p38 mitogen-activated proteinkinase. Electrophoretic mobility shift assays with oligonucleotides containing one of the two AP-1 binding sites showed that glucose treatment markedly enhanced the binding activity of nuclear proteins of mesangial cells, particularly to box B. Supershift assays demonstrated that JunD and c-Fos were present in the protein-DNA complexes under control and hyperglycemic conditions. The functional and structural results show that glucose regulates human TGF-β1 gene expression through two adjacent AP-1 binding sites and gives rise to the involvement of protein kinase C and p38 mitogen-activated proteinkinase in hyperglycemia-induced TGF-β1 gene expression.
Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis
Authors: Jasper J. Haringman, Danielle M. Gerlag, Aeilko H. Zwinderman, Tom J.M. Smeets, Maarten C. Kraan, Dominique Baeten, Iain B. McInnes, Barry Bresnihan, Paul Peter Tak
Journal: Annals of the Rheumatic Diseases (2004)

Previous work identified synovial sublining macrophage numbers as a potential biomarker for clinical efficacy in rheumatoid arthritis.To investigate the association between changes in infiltration of synovial macrophages and clinical improvement after antirheumatic treatment.88 patients who participated in various clinical trials were studied. All patients underwent serial arthroscopy before initiation of treatment and after different time intervals. Immunohistochemical and digital image analysis were performed according to standardised procedures to detect changes in CD68+ synovial sublining macrophages in relationship to changes in the 28 joint count Disease Activity Score (DAS28). Statistical analysis was performed using one way analysis of variance, the independent samples t test, linear regression, and the standardised response mean (SRM).For good, moderate, and non-responders, according to the DAS28 response criteria, there was a significant difference in the change in sublining macrophages (mean (SEM) cells/mm(2) -643 (124), -270 (64), and -95 (60), respectively; p<0.0003). There was a significant correlation between the change in the number of macrophages and the change in DAS28 (Pearson correlation 0.874, p<0.01). The change in sublining macrophages explained 76% of the variation in the change in DAS28 (p<0.02). The sensitivity to change of the biomarker was high in patients treated actively (SRM >0.8), whereas the ability to detect changes in placebo treated patients was weak (SRM <0.3).The results suggest that changes in synovial sublining macrophages can be used to predict possible efficacy of antirheumatic treatment.
Diagnostic Thoracotomy for Solid Pulmonary Infiltrates
Authors: E. Husfeldt, C. J. Carlsen
Journal: Thorax (1950)

The progress of thoracic surgery within the last decade has solved many important problems, but it has also posed others.One of these is the correct attitude towards that group of patients who previously were kept under observa- tion, namely, those who exhibit a round, sharply demarcated, solid shadow in the lung field as a chance finding (for example, in a routine radiograph or at mass- radiography) without subjective or objective symptoms.This study does not include cases in which the radiological appearances suggested lesions issuing from the mediastinum or from the chest wall.These cases have been well known for a long time, but they are now being detected in larger numbers because of the increased use of chest radiography and more particularly of mass radiography.With the diagnostic means available to-day it is possible to make an exact diagnosis in almost every case of haemoptysis, persistent cough, dyspnoea, thoracic pain, but in most of these symptomless cases it is impossible to decide the nature of the disease, even when all modern diagnostic means are utilized.For these reasons it was decided, in 1942, to operate in such cases unless there were serious contraindications to surgery.Within other fields of surgery exploratory interventions are accepted in obscure cases.In our opinion, the risk involved by exploratory thoracotomy is slight in view of the present stage of operative technique, anaesthesia, and pre-and post- operative treatment.In addition, these patients stand exploratory thoracotomy much better than patients with clinically manifest malignancies.This series of 33 patients is " selected " because it includes patients who have entered the hospital after a long or short period of observation elsewhere, usually because they have been suspected of malignancy on the basis of the radiological findings and their age.This study affords no data as to the incidence of the con- dition among the population as a whole and no conclusion as to the procedure of choice in " young " patients, that is, those under about 35 years of age.It is common to all the patients that they exhibited a pulmonary shadow of the kind described above, had no symptoms, and failed to show any other signs of diagnostic value after Wassermann tests, examinations of the sputum for tubercle bacilli and tumour cells, bronchoscopy, and extended radiological examinations.The sex and age distribution as well as the post-operative diagnosis are tabulated.At the present time it may be said that our principle of treatment was justified by demonstrating four early cases of carcinoma, and these were considered to have a better prognosis than patients who underwent operation after symptoms had on July 13, 2023 by guest.
Renal F4/80+CD11c+ Mononuclear Phagocytes Display Phenotypic and Functional Characteristics of Macrophages in Health and in Adriamycin Nephropathy
Authors: Qi Cao, Yiping Wang, Xin Maggie Wang, Junyu Lu, Vincent W.S. Lee, Qianling Ye, Hanh Nguyen, Guoping Zheng, Ye Zhao, Stephen I. Alexander, David C.H. Harris
Journal: Journal of the American Society of Nephrology (2014)

Conventional markers of macrophages (Mфs) and dendritic cells (DCs) lack specificity and often overlap, leading to confusion and controversy regarding the precise function of these cells in kidney and other diseases. This study aimed to identify the phenotype and function of renal mononuclear phagocytes (rMPs) expressing key markers of both Mфs and DCs. F4/80+CD11c+ cells accounted for 45% of total rMPs in normal kidneys and in those from mice with Adriamycin nephropathy (AN). Despite expression of the DC marker CD11c, these double-positive rMPs displayed the features of Mфs, including Mф-like morphology, high expression of CD68, CD204, and CD206, and high phagocytic ability but low antigen-presenting ability. F4/80+CD11c+ cells were found in the cortex but not in the medulla of the kidney. In AN, F4/80+CD11c+ cells displayed an M1 Mф phenotype with high expression of inflammatory mediators and costimulatory factors. Adoptive transfer of F4/80+CD11c+ cells separated from diseased kidney aggravated renal injury in AN mice. Furthermore, adoptive transfer of common progenitors revealed that kidney F4/80+CD11c+ cells were derived predominantly from monocytes, but not from pre-DCs. In conclusion, renal F4/80+CD11c+ cells are a major subset of rMPs and display Mф-like phenotypic and functional characteristics in health and in AN.
Why Academic Divisions of Hematology/Oncology Are in Trouble and Some Suggestions for Resolution
Authors: Thomas J. Smith, John Girtman, Jerry Riggins
Journal: Journal of Clinical Oncology (2001)

Academic divisions of hematology/oncology seem to have difficulty recruiting and retaining excellent productive clinicians. A major reason for this is that salaries do not compete with the private sector for similar work.We reviewed divisional finances productivity, and experiences from faculty members leaving.The academic salaries are approximately one third of practice because the chemotherapy concession has been given to the academic hospital. In addition, there may be substantial problems in under-billing, lack of attention to detail in billing, and poor collection practices.Academic practice still has much to offer, including opportunities for research and multidisciplinary team management, although the differences may narrow over the coming years. Attention to detail in the billing, collection for work performed, and increasing academic salaries to levels nearer to private practice are necessary components of the solution to recruit and retain quality productive clinicians.
678 Effect of 6h exposure to 50ppb ozone (O3) on release of IL-8 and RANTES from nasal epithelial cells (NEC) from atopic rhinitics and the influence of fluticasone propionate (FP), in vitro
Authors: M CALDERON, J DEVALIA, A PRIOR, R DAVIES
Journal: Journal of Allergy and Clinical Immunology (1996)
Sulfonamide Reactions in Systemic Lupus Erythematosus
Authors: Phin Cohen
Journal: JAMA (1966)

WITHIN the past five years we have seen four cases of systemic lupus erythematosus (SLE) in which relapse was associated with administration of sulfonamide drugs. Although the warnings relating sulfonamide therapy to apparent initiation or to exacerbation of SLE have been sounded intermittently for three decades,<sup>1-7</sup>we are reporting these cases for two reasons: (1) The textbooks of medicine<sup>2</sup>and a recent monograph on SLE<sup>3</sup>do not emphasize this phenomenon. (2) The proliferation of sulfonamide-related pharmacological agents (for example, acetazoleamide, tolbutamide, chlorothiazide) may, in fact, represent a potential menance for SLE-susceptible persons. The preventive medicine aspects of this problem need reemphasis. The patients were from the medical service of the Peter Bent Brigham Hospital. The lupus erythematosus (LE) cell test and the fluorescent antibody test were done by standard methods. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 39-year-old woman presented with a three-year history of intermittent joint stiffness;
Chronic pancreatitis and mutations of the cystic fibrosis gene
Authors: C J TAYLOR
Journal: Gut (1999)

Background: The pancreatic lesions of cystic fibrosis develop in utero and closely resemble those of chronic pancreatitis.Therefore, we hypothesized that mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may be more common than expected among patients with chronic pancreatitis.Methods: We studied 134 consecutive patients with chronic pancreatitis (alcohol-related disease in 71, hyperparathyroidism in 2, hypertriglyceridemia in 1, and idiopathic disease in 60).We examined DNA for 22 mutations of the CFTR gene that together account for 95 percent of all mutations in patients with cystic fibrosis in the northwest of England.We also determined the length of the noncoding sequence of thymidines in intron 8, since the shorter the sequence, the lower the proportion of normal CFTR messenger RNA.Results: The 94 male and 40 female patients ranged in age from 16 to 86 years.None had a mutation on both copies of the CFTR gene.Eighteen patients (13.4 percent), including 12 without alcoholism, had a CFTR mutation on one chromosome, as compared with a frequency of 5.3 percent among 600 local unrelated partners of persons with a family history of cystic fibrosis (P<0.001).A total of 10.4 percent of the patients had the 5T allele in intron 8 (14 of 134), which is twice the expected frequency (P=0.008).Four patients were heterozygous for both a CFTR mutation and the 5T allele.Patients with a CFTR mutation were younger than those with no mutations (P=0.03).None had the combination of sinopulmonary disease, high sweat electrolyte concentrations, and low nasal potential-diVerence values that are diagnostic of cystic fibrosis.Conclusions: Mutations of the CFTR gene and the 5T genotype are associated with chronic pancreatitis.
The Immunomodulatory Benzodiazepine Bz-423 Inhibits B-Cell Proliferation by Targeting c-Myc Protein for Rapid and Specific Degradation
Authors: Thomas B. Sundberg, Gina M. Ney, Chitra Subramanian, Anthony W. Opipari, Gary D. Glick
Journal: Cancer Research (2006)

Abstract Myc proteins regulate cell growth and are oncogenic in many cancers. Although these proteins are validated molecular anticancer targets, new therapies aimed at modulating myc have yet to emerge. A benzodiazepine (Bz-423) that was discovered in efforts to find new drugs for lupus was found recently to have antiproliferative effects on Burkitt's lymphoma cells. We now show that the basis for the antiproliferative effects of Bz-423 is the rapid and specific depletion of c-myc protein, which is coupled to growth-suppressing effects on key regulators of proliferation and cell cycle progression. c-Myc is depleted as a result of signals coupled to Bz-423 binding its molecular target, the oligomycin sensitivity-conferring protein subunit of the mitochondrial F1Fo-ATPase. Bz-423 inhibits F1Fo-ATPase activity, blocking respiratory chain function and generating superoxide, which at growth-inhibiting concentrations triggers proteasomal degradation of c-myc. Bz-423-induced c-myc degradation is independent of glycogen synthase kinase but is substantially blocked by mutation of the phosphosensitive residue threonine 58, which when phosphorylated targets c-myc for ubiquitination and subsequent proteasomal degradation. Collectively, this work describes a new lead compound, with drug-like properties, which regulates c-myc by a novel molecular mechanism that may be therapeutically useful. (Cancer Res 2006; 66(3): 1775-82)
Functional Divergence for Every Paralog
Authors: Patricia S. Soria, Kriston L. McGary, Antonis Rokas
Journal: Molecular Biology and Evolution (2014)

Because genes can be constrained by selection at more than one phenotypic level, the relaxation of constraints following gene duplication allows for functional divergence (FD) along multiple phenotypic axes. Many studies have generated individual measures of FD, but the profile of FD between paralogs across levels of phenotypic space remains largely uncharted. We evaluate paralog pairs that originated via the yeast whole-genome duplication (ohnolog pairs) at three distinct phenotypic levels (properties of proteins, gene expression, and overall organismal growth) using eight complementary measures of FD (protein: evolutionary rates, radical amino acid substitutions, and domain architecture; gene expression: expression differences in a single species and condition, across species in a single condition, and in a single species across conditions; and organismal: genetic interaction profiles and growth profiles in multiple conditions). We find that the majority of ohnolog pairs show FD by multiple phenotypic measures. Within each phenotypic level, measures of FD are strongly correlated but are generally weakly correlated between levels, suggesting that functional constraints exerted on genes from distinct phenotypic levels are largely decoupled. Our results suggest that redundancy is a rare functional fate for retained paralogs and that FD cannot be fully captured by measures at any single phenotypic level.
Suppression of anti-glomerular basement membrane nephritis by administration of anti-monocyte chemoattractant protein-1 antibody in WKY rats.
Authors: H Fujinaka, T Yamamoto, M Takeya, L Feng, K Kawasaki, E Yaoita, D Kondo, C B Wilson, M Uchiyama, I Kihara
Journal: Journal of the American Society of Nephrology (1997)

Anti-glomerular basement membrane (GBM) nephritis in WKY rats is characterized by an accumulation of CD8-positive lymphocytes (CD8+ lym) and monocytes/macrophages (Mo/M psi) in the glomeruli and crescent formation. In the study presented here, the involvement of a chemokine for Mo/M psi, monocyte chemoattractant protein-1 (MCP-1), was examined in this model. An intense induction of mRNA for MCP-1 in the glomeruli and a suppressive effect of anti-MCP-1 antibody administration on the glomerular Mo/M psi accumulation and proteinuria were found. MCP-1 mRNA was expressed intensely in the glomeruli 4 d after the anti-GBM antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of Mo/M psi infiltrating in the glomeruli decreased by 34.7% (19.6 +/- 7.1 versus 30.0 +/- 6.0 per glomerular cross-section, P < 0.01) and proteinuria by 66.2% (15.6 +/- 9.3 versus 46.1 +/- 15.1 mg/d, P < 0.01) at day 4. In contrast, the number of CD8+ lym accumulating in the glomeruli was not affected significantly (6.6 +/- 2.7 versus 6.0 +/- 3.0 per glomerular cross-section, P > 0.05). However, the treatment with the anti-MCP-1 antibody did not reduce Mo/M psi infiltration, urinary protein excretion, and crescent formation at day 8. These data suggest that MCP-1 plays a role in the glomerular accumulation of Mo/M psi, and that the infiltrating Mo/M psi cause glomerular injury and increased excretion of protein in the urine.
Potential Prostate Cancer Drug Target: Bioactivation of Androstanediol by Conversion to Dihydrotestosterone
Authors: James L. Mohler, Mark A. Titus, Elizabeth M. Wilson
Journal: Clinical Cancer Research (2011)

Abstract High-affinity binding of dihydrotestosterone (DHT) to the androgen receptor (AR) initiates androgen-dependent gene activation, required for normal male sex development in utero, and contributes to prostate cancer development and progression in men. Under normal physiologic conditions, DHT is synthesized predominantly by 5α-reduction of testosterone, the major circulating androgen produced by the testis. During androgen deprivation therapy, intratumoral androgen production is sufficient for AR activation and prostate cancer growth, even though circulating testicular androgen levels are low. Recent studies indicate that the metabolism of 5α-androstane-3α, 17β-diol by 17β-hydroxysteroid dehydrogenase 6 in benign prostate and prostate cancer cells is a major biosynthetic pathway for intratumoral synthesis of DHT, which binds AR and initiates transactivation to promote prostate cancer growth during androgen deprivation therapy. Drugs that target the so-called backdoor pathway of DHT synthesis provide an opportunity to enhance clinical response to luteinizing-hormone–releasing hormone (LHRH) agonists or antagonists, AR antagonists, and inhibitors of 5α-reductase enzymes (finasteride or dutasteride), and other steroid metabolism enzyme inhibitors (ketoconazole or the recently available abiraterone acetate). Clin Cancer Res; 17(18); 5844–9. ©2011 AACR.
Controlling U.S. Health Care Spending — Separating Promising from Unpromising Approaches
Authors: Peter S. Hussey, Christine Eibner, M. Susan Ridgely, Elizabeth A. McGlynn
Journal: New England Journal of Medicine (2009)

High U.S. health care spending has been characterized not only as a barrier to affordable insurance but also as the preeminent long-term threat to the economy and the competitiveness of American business. The current policy discussion in Congress does not address this problem. The search for government savings with which to fund coverage expansions makes public programs the main targets for spending reductions; opportunities for private-sector savings are left out of the equation. We think it is useful to consider the cost-control options available to both the public and the private sectors.Although there is no consensus on what should . . .
Aspirin and Arteriovenous Graft Thrombosis in Hemodialysis
Authors: Fritz R. Bech, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2011)

The Center for Medicare and Medicaid Services' (CMS) Fistula First initiative has changed dialysis practice. In 2003, more than one third (37%) of patients on hemodialysis (HD) used prosthetic arteriovenous grafts (AVGs), slightly more than the 35% using native AV fistulas (AVFs). By 2010, fewer
Hospital management of adults with severe acute respiratory syndrome (SARS) if SARS re-emerges—updated 10 February 2004
Authors: W.S Lim, S.R Anderson, R.C Read
Journal: Journal of Infection (2004)

Severe Acute Respiratory Syndrome (SARS) is a potentially severe and highly infectious disease to which healthcare workers involved in the management of cases are particularly vulnerable. These guidelines briefly summarise optimal and safe practice for clinicians involved in the emergency care of patients with probable or confirmed SARS.
Mechanisms of Self-Motion Perception
Authors: Kenneth H. Britten
Journal: Annual Review of Neuroscience (2008)

Guiding effective movement through the environment is one of the visual system's most important functions. The pattern of motion that we see allows us to estimate our heading accurately in a variety of environments, despite the added difficulty imposed by our own eye and head movements. The cortical substrates for heading perception include the medial superior temporal area (MST) and the ventral intraparietal area (VIP). This review discusses recent work on these two areas in the context of behavioral observations that establish the important problems the visual system must solve. Signals relevant to self motion are both more widespread than heretofore recognized and also more complex because they are multiplexed with other sensory signals, such as vestibular, auditory, and tactile information. The review presents recent work as a background to highlight important problems that remain unsolved.