tbuckley/cabot-search huggingface dataset:
The adaptive stroma joining the antiangiogenic resistance front
Authors: Oriol Casanovas
Journal: Journal of Clinical Investigation (2011)

Resistance to antiangiogenic therapies in cancer involves both tumor cells and stromal components, but their relative contributions differ in each cancer subtype. In this issue of the JCI, Cascone et al. describe a stromal adaptation to antiangiogenic therapy in non–small cell lung carcinoma (NSCLC) models that include EGFR-driven vascular remodeling promoting resistance to VEGF inhibition. Their results suggest that the added benefit of dual VEGF/R and EGFR targeting in these models could be clinically relevant to fight resistance in NSCLC patients.
Maturation of aldose reductase expression in the neonatal rat inner medulla.
Authors: G J Schwartz, B J Zavilowitz, A D Radice, A Garcia-Perez, J M Sands
Journal: Journal of Clinical Investigation (1992)

Newborns are less able to concentrate urine than adults are. With development of the concentrating system and a hypertonic medullary interstitium, there is a need to generate intracellular osmolytes such as sorbitol, which is produced in a reaction catalyzed by the enzyme aldose reductase. We sought to discriminate between two possible mechanisms of aldose reductase induction during development: (a) a response to an osmotic stimulus generated by the concentrating mechanism; or (b) part of the genetic program for development of the kidney. We measured the change in aldose reductase mRNA and activity in terminal inner medullary collecting ducts (IMCDs) microdissected from Sprague-Dawley rats during the first month of life. Aldose reductase mRNA was assayed by Northern analysis of total RNA from inner medulla and by detection of the reverse transcription-polymerase chain reaction (RT-PCR) product obtained from single IMCDs using aldose reductase-specific primers. Aldose reductase activity was measured in IMCDs taken from the same rats using a fluorescent microassay. Newborn rat IMCDs had minimal aldose reductase mRNA or activity, however mRNA was readily detected in IMCDs from rats older than 3 d of age, with peak expression occurring at 1-3 wk of age before decreasing to adult levels. In contrast, the mRNA level for a housekeeping metabolic enzyme, malate dehydrogenase, did not change during maturation. Aldose reductase enzyme activity was readily detectable by 6 d of age, peaked at 20 d, then decreased to adult levels. Urine osmolality remained < 600 mosmol/kg until 16 d, then increased to > 1,100 mosmol/kg after 20 d. Thus, aldose reductase mRNA and activity increased before urinary osmolality reached 870 mosmol/kg. Because urine osmolality may not be indicative of inner medullary osmolality and because mother's milk may provide excessive free water to the pups under 3 wk of age, half of the animals in several litters were separated from their mothers for 1 d and inner medullary osmolality, in addition to urine osmolality, was measured by vapor pressure osmometry, while aldose reductase mRNA was assessed densitometrically in IMCDs after RT-PCR. Although fluid restriction resulted in a near doubling of urine osmolality and a tendency towards increased aldose reductase mRNA, there was no consistently significant increase in aldose reductase mRNA or inner medullary osmolality during the first 13 d of life compared to the suckling animals. On the other hand, 2-3-wk-old rats showed significant increases in aldose reductase mRNA, accompanied by increases in inner medullary osmolality, after fluid restriction. Thus, the dissociation between the increases in aldose reductase expression and inner medullary hyperosmolality indicates that the maturational induction of the aldose reductase gene is not a consequence of osmotic stimulation, but rather, part of the developmental program of the kidney.
THE TUBERCULOUS TONSIL
Authors: ROBERT LEVY
Journal: JAMA (1910)

In 1886 Trautman<sup>1</sup>made the statement that children of tuberculous parents suffering from hyperplasia of the pharyngeal tonsil showed marked local and general reactions following the injection of tuberculin, the continued use of which resulted in cure of the hyperplasia. From this he argued that such tonsillar affections were tuberculous. It was not, however, until 1895 that any serious attempt was made to prove by laboratory investigation the relationship between hypertrophy of the pharyngeal and faucial lymphoid tissue and tuberculosis. At this time intense interest was awakened by the experiments of Dieulafoy,<sup>2</sup>and, although it has since been shown that these experiments could not be considered conclusive, the interest awakened thereby resulted in the development of an enormous literature, much experimentation and more or less conclusive as well as confusing reports. To a clinician accustomed to using laboratory methods only for purposes of confirming diagnoses made from subjective
False positive results of tests for syphilis and outcome of pregnancy: a retrospective case-control study.
Authors: J G Thornton, G A Foote, C E Page, A D Clayden, L A Tovey, J S Scott
Journal: BMJ (1987)

In a retrospective case-control study 64 women yielding a false positive result to a test for syphilis in pregnancy were compared with 128 controls individually matched for age, parity, hospital of delivery, and year of delivery. There were significantly more unsuccessful pregnancies, mainly spontaneous abortions during the first and second trimesters, among women with persistent false positive results. There was no significant difference between groups in the mean birth weights of liveborn infants. The antibodies responsible for the false positive result may indicate the presence of an immunological disturbance. Women who give a false positive result should be carefully managed throughout their pregnancy.
Combined Propranolol and Digoxin Therapy in Angina Pectoris
Authors: MICHAEL H. CRAWFORD
Journal: Annals of Internal Medicine (1975)

The effects of oral propranolol and digoxin alone and in combination on angina frequency, heart size, systolic time intervals and treadmill exercise tolerance, were assessed in 20 patients with coronary heart disease. Oral propranolol alone reduced the average frequency of angina pectoris from 16 to 7 attacks per week (P < 0.02). However, the mean duration of exercise was not significantly improved because 8 patients with abnormal left ventricular function exhibited a decrease in exercise tolerance. Combined propranolol and digoxin improved exercise tolerance in these patients, and, consequently, mean exercise duration in all patients increased significantly from the control value of 390 ± 42 to 458 ± 46 s (P < 0.01). Propranolol alone also resulted in a significant increase in left heart size from 46.5 ± 1.3 to 47.7 ± 1.5 mm/m2 (P < 0.001), which was reversed by the addition of digoxin. Therefore, oral propranolol combined with digoxin is advantageous in patients with angina pectoris who have abnormal ventricular function or large hearts.
C/EBP ? isoforms LIP and LAP modulate progression of the cell cycle in the regenerating mouse liver
Authors: Tom Luedde, Moritz Duderstadt, Konrad L. Streetz, Frank Tacke, Stefan Kubicka, Michael P. Manns, Christian Trautwein
Journal: Hepatology (2004)

The CCAAT enhancer-binding protein (C/EBP) β gene can produce several N-terminally truncated isoforms. Liver-enriched activator protein (LAP) is a transcriptional activator in many systems, whereas liver-enriched inhibitory protein (LIP) is regarded as a functional LAP antagonist. In this study, we examined the impact of these two proteins on cell cycle progression in the regenerating liver. Adenoviral overexpression of LAP, in addition to its role as a transactivator of liver-specific genes, led to a delayed S-phase entry of hepatocytes after partial hepatectomy (PH) in vivo . This delay was accompanied by decreased expression of cyclin A and E as well as proliferating cell nuclear antigen and decreased cyclin-dependent kinase 2 activity at the G1/S boundary. This observation is not explained by increased p21 CIP1/Waf1 expression or lack of phosphorylation of external LAP, but LAP overexpression triggered a decreased C/EBP-α/C/EBP-α-30 ratio and a reduced basal c-jun level in the liver. In contrast, adenoviral overexpression of LIP resulted in a stronger and earlier induction of cyclin A and E after PH, but did not change the timing and extent of cyclin-dependent kinase 2 activity or the amount of hepatocytes that entered S phase in this model. In the LIP expressing group, both C/EBP-α isoforms and c-jun were more strongly induced after PH. In conclusion , the LAP/LIP ratio is an important modulator of cell cycle progression during liver regeneration. In the context of previous studies, our results demonstrate that LAP, through a dose-dependent effect, withholds a dual activating and inhibiting role on hepatocyte proliferation in vivo . (Hepatology 2004;40:356-365.)
Oral administration of human serum immunoglobulin in immunodeficient patients with viral gastroenteritis. A pharmacokinetic and functional analysis.
Authors: G A Losonsky, J P Johnson, J A Winkelstein, R H Yolken
Journal: Journal of Clinical Investigation (1985)

We examined the pharmacokinetics and immunological activity of human serum immunoglobulins (HSG) possessing anti-rota-virus activity which were orally administered to three children with primary immunodeficiency syndromes and prolonged gastrointestinal excretion of rotavirus. Detailed analysis of the excretion of immunoglobulins labeled with biotin or I125 revealed that approximately 50% of the recovered radioactivity was excreted in the stools over a 3-d period. Approximately half of the excreted radioactivity recovered in the stool was in a macromolecular form with immunological activity. The remainder of the recovered radioactivity was excreted in the urine as low molecular weight fragments or free iodide. In addition, immunological and chromatographic analyses revealed that the oral administration of HSG resulted in the generation of rotavirus-specific immune complexes in the gastrointestinal tract with a subsequent decrease in the presence of uncomplexed rotavirus antigen. These studies indicate that orally administered HSG can survive passage in the gastrointestinal tract in an immunologically active form, and that the oral administration of immunoglobulins with specific reactivities has potential for the prevention or treatment of gastrointestinal infections.
A Precarious Exchange
Authors: Siddhartha Mukherjee
Journal: New England Journal of Medicine (2004)

If an anthropologist were to stumble into this room between 6 and 8 p.m. this evening, he might find the telltale signs of a ritual: a group of residents and interns huddled around a table, scribbling hieroglyphics on scraps of paper.(Figure)To a physician, this scenario is all too familiar — we call it "sign-out" — but in a way, the anthropologist would be right: it is a peculiar ritual, this daily transfer of patients from one medical team to another. As I write this, at the end of a frantic afternoon, 18 residents are simultaneously handing off . . .
Insulin Use in NIDDM
Authors: Saul Genuth
Journal: Diabetes Care (1990)

The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein. Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function. These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality. Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms. In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin. A key goal of insulin therapy is to normalize the fasting plasma glucose level. In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime. Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control. In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both. However, long-term benefits from such combination therapy remain to be demonstrated conclusively. Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain. Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia. Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial. A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension. Although potential mechanisms for an atherogenic action of insulin exist, current evidence does not prove cause and effect and does not warrant withholding insulin therapy (or compromising on dosage) when it is needed.
Abstract 4919: Pathway profiling of head and neck cancer cell lines
Authors: Zhixiang Zuo, Johannes Braegelmann, Michaela Keck, Wanda Shen, Mohamed El Dinali, Everett E. Vokes, Tanguy Y. Seiwert
Journal: Cancer Research (2012)

Abstract Introduction: Cell lines retain key genetic aberrations of the originating tumors, which frequently correlate with sensitivity to specific inhibitors. We performed genetic and pathway based profiling of 40 head and neck cancer (HNC) cell lines using three publicly available methods for pathway profiling based on expression and copy number data. Methods: 40 HNC cell lines were analyzed for expression using expression arrays (Agilent), and copy number using array comparative hybridization (aCGH) and/or Nanostring methodologies. Integrative genomic analysis was performed to determine pathway activity using pathway analysis techniques previously described by Gatza et al. (BFRM), Pe'er et al (CONEXIC), Vaske et al. (PARADIGM). Results: Frequent pathway activation was identified in &amp;gt;10 well established signalling pathways for HNC including TP53, PI3K-AKT, TP63/SOX2, Cyclin D1, MYC etc, as well as several - for HNC previously unknown - signalling pathways. Cell lines could be associated with expression-based biologic subtypes in HNC tissues suggesting that specific cell lines should be used preferentially for modelling and therapeutic evaluation for HNC subtypes (including HPV(+) cell lines with characteristics of HPV(+) tumors). The three pathway analysis platforms identified a large number of pathways with some overlap in particular between BFRM and CONEXIC, whereas PARADIGM profiled a much wider set of pathways. Both CONEXIC and PARADIGM employed copy number data, whereas BFRM relied solely on expression data. Conclusion: Pathway alterations characteristic of head and neck cancers were identified in virtually all HNC cell lines. Pathway based classification of cell lines was achieved and correlated with pathway activity in HNC tumor tissues. Three pathway-profiling approaches provided a large set of pathway activity with some significant overlap that may have translational relevance. Validation studies are currently on-going. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4919. doi:1538-7445.AM2012-4919
Metabolism of [1-(14)C] and [2-(14)C] leucine in cultured skin fibroblasts from patients with isovaleric acidemia. Characterization of metabolic defects.
Authors: K Tanaka, R Mandell, V E Shih
Journal: Journal of Clinical Investigation (1976)

Leucine metabolism in cultured skin fibroblasts from patients with isovaleric acidemia was compared with that in normal fibroblasts and in cells from patients with maple syrup urine disease using [1-(14)C] and [2-(14)C] leucine as substrates. Inhibitory effects of methylenecyclopropylacetic acid on leucine metabolism in normal cells were also investigated. Production of 14CO2 from [2-(14)C] leucine was very reduced (96-99%) in both types of mutant cells. Radioactive isovaleric acid accumulated in assay media with isovaleric acidemia cells but not in those with maple syrup urine disease cells. Unexpectedly, 14CO2 production from [1-(14)C] leucine was partially depressed (80%) in isovaleric acidemia cells whereas in maple syrup urine disease cells it was strongly depressed (99%) as expected. These two mutant cells were clearly distinguished by detection of 14C-isovaleric acid accumulation after incubation with [2-(14)C] leucine. A pattern of inhibition of leucine oxidation similar to that seen in isovaleric acidemia cells was induced in normal cells by the addition of 0.7 mM methylenecyclopropylacetic acid to the assay medium. The partial inhibition of [1-(14)C] leucine oxidation seen in isovaleric acidemia cells and also in normal cells in the presence of the inhibitor appears to be, at least in part, due to an accumulation of isovalerate in the cells. Isovaleric acid (5-10) mM) inhibited [1-(14)C] leucine oxidation 32-68% when added to the assay medium with normal cells. Addition of flavin adenine dinucleoside to culture medium or assay medium or both did not restore oxidation of either leucine substrate in isovaleric acidemia cells.
Antibodies of patients with Lyme disease to components of the Ixodes dammini spirochete.
Authors: A G Barbour, W Burgdorfer, E Grunwaldt, A C Steere
Journal: Journal of Clinical Investigation (1983)

Lyme disease is an inflammatory disorder of skin, joints, nervous system, and heart. The disease is associated with a preceding tick bite and is ameliorated by penicillin treatment. A spirochete (IDS) isolated from Ixodes dammini ticks has been implicated as the etiologic agent of Lyme disease. We examined the antibody responses of Lyme disease patients to IDS lysate components in order to further understand the pathogenesis of this disease. The components were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, reacted with patients' sera, and the bound IgG was detected with 125I-labeled protein A (western blot). We found that (a) Lyme disease patients had antibodies to IDS components (b) most patients studied had antibodies to two components with apparent subunit molecular weights of 41,000 and 60,000, and (c) the patients' antibody responses during illness and remission were specific, for the most part, for the IDS. In contrast to the findings with Lyme disease sera, sera from controls showed little reactivity with IDS components in either the western blots or a derivative solid-phase radioimmunoassay.
Nephrotoxicity of Cyclosporin a after Allogeneic Marrow Transplantation
Authors: Howard Shulman, Gary Striker, Michael Kennedy, Rainer Storb, E. Donnall Thomas
Journal: New England Journal of Medicine (1981)

CYCLOSPORIN A, a fungal metabolite, is a potent new immunosuppressive drug1 , 2 that has been reported to prevent or ameliorate rejection of kidney and liver allografts3 4 5 and graft-versus-host disease after allogeneic marrow transplantation.6 , 7 A potentially harmful side effect of therapy with cyclosporin A is renal toxicity. Previous reports of nephrotoxicity after cyclosporin A have emphasized the mild and transient elevations of blood urea nitrogen (BUN) and creatinine.3 4 5 6 7 8 9 We now describe a distinct histologic constellation of glomerular thromboses and severe tubular damage, which correlated with the clinical course and laboratory findings of severe renal failure in three recipients of allogeneic marrow who . . .
Cardiac Arrythmia During Oral Surgery
Authors: Clyde W. Jones
Journal: JAMA (1969)

To the Editor:—  In Cardiac Arrhythmias During Oral Surgery With Halothane-Nitrous-Oxide (Oxygen Anesthesia by Fisch et al (208:1839, 1969), the authors reported an incidence of arrhythmias of 42.7%. This would certainly be an unusually high incidence with a welladministered anesthetic in which adequate depth, intubation of the trachea, and ventilatory support are accomplished, as is done in the operating room for more involved oral surgical procedures. In lightly anesthetized patients, with surgery being performed on the upper portion of the airway and anethesia being administered without intubation through a demand nonrebreathing system, a high incidence of arrhythmias can certainly be expected. Lightness of anesthetic depth and carbon dioxide buildup must be considered as significant contributing factors.  I firmly agree that this is not the best technique to be used routinely in this type of situation. I would further state that not only this technique butno form of anesthesia
Acute myelogenous leukemia in a patient with Li–Fraumeni syndrome treated with valproic acid, theophyllamine and all-trans retinoic acid: a case report
Authors: N Ånensen, J Skavland, C Stapnes, A Ryningen, A-L Børresen-Dale, B T Gjertsen, Ø Bruserud
Journal: Leukemia (2006)
When News in the<i>Journal</i>Is News
Authors: F.J. Ingelfinger
Journal: New England Journal of Medicine (1975)

Among the complaints that the Journal receives with less than infrequent frequency (an admirable ambiguity patterned after certain medical accounts), one that turns up every so often runs somewhat like this:"Whenever the Journal publishes material of exceptional general interest or clinical importance, how do I hear about it first? From one of my patients! In addition, he is apt to ask why he is not receiving this effective new treatment, or why he is receiving this new treatment now identified as ineffective. The patient found the information in his morning newspaper, but I am too busy for that sort . . .
The Relationship between Intrinsic Coagulation Pathway and Cardiac Syndrome X Development in Patients with Diabetes Mellitus
Authors: Mehmet Vefik Yazıcıoğlu, Ulaankhuu Batgerel, Murat Yüksel, Göksel Açar, Gamze Babür Güler, Ali Metin Esen, Soe Moe Aung, Mustafa Tabakçı, Cüneyt Toprak, Mehmet Muhsin Türkmen
Journal: Journal of the American College of Cardiology (2013)
Severe Degenerative Joint Disease
Authors: Gerald S. Gilchrist
Journal: JAMA (1977)

Severe degenerative joint disease developed in three adults with mild to moderately severe hemophilia A, as judged by the clinical course and by levels of factor VIII coagulant. Bilateral total hip arthroplasty was required in one patient, unilateral hip arthroplasty in the second, and a recommendation for bilateral knee replacement in the third. The pathogenesis of the arthropathy may be multifactorial and the result of repeated joint hemorrhage that remains unrecognized and inadequately treated. These observations suggest the need for more careful monitoring of patients who have relatively mild hemophilia.
Autologous mixed lymphocyte reaction is reduced in patients with psoriasis
Authors: T. TERUI, M. ROKUGO, S. AIBA, T. KATO, H. TAGAMI
Journal: British Journal of Dermatology (1990)

The autologous mixed lymphocyte reaction (auto‐MLR) was studied to test the interactions between immunocompetent cells in patients with psoriasis. The auto‐MLR in 20 patients with psoriasis was significantly lower than in 16 normal controls. Lower values were found in untreated psoriatic patients than in those in remission following treatment. The values in the latter group were significantly lower than in controls and in six patients with atopic dermatitis in remission. The tendency for an increase in the auto‐MLR with a decrease in disease activity was further confirmed in five patients studied before and after treatment. In contrast, the allogeneic lymphocyte reaction (allo‐MLR) in psoriatics was similar to that in normal controls.