tbuckley/cabot-search huggingface dataset:
Incorporating Bortezomib into the Treatment of Lung Cancer
Authors: Angela M. Davies, Primo N. Lara, Philip C. Mack, David R. Gandara
Journal: Clinical Cancer Research (2007)

Abstract Bortezomib, a small-molecule proteasome inhibitor, has activity in lung cancer both as a single agent and in combination with agents commonly used in lung cancer. The ability of bortezomib to favorably modulate the expression of apoptosis-associated proteins, along with its moderate toxicity as a single agent, provides the basis for its combination with cytotoxic agents in the treatment of lung cancer. In non–small cell lung cancer, bortezomib as a single agent has limited activity but in combination with chemotherapy has shown encouraging activity without significantly adding to toxicity. Bortezomib as a single agent has shown minimal activity in small cell lung cancer. Although the role of bortezomib in lung cancer is uncertain, it is likely to have its greatest clinical benefit when given in combination with other therapeutics. Ongoing studies are focused on optimizing the scheduling of bortezomib with chemotherapy, investigating its combination with targeted agents and radiation, and examining its efficacy in a specific subgroup, bronchioloalveolar carcinoma.
Effects of inorganic iron and myoglobin on in vitro proximal tubular lipid peroxidation and cytotoxicity.
Authors: R A Zager, C A Foerder
Journal: Journal of Clinical Investigation (1992)

Recent in vivo studies suggest that heme Fe causes proximal tubular lipid peroxidation and cytotoxicity, thereby contributing to the pathogenesis of myoglobinuric (Mgb) acute renal failure. Because hydroxyl radical (.OH) scavengers [dimethylthiourea (DMTU), benzoate, mannitol] can mitigate this injury, it is postulated that .OH is a mediator of Mgb-induced renal damage. The present study has tested these hypotheses using an isolated rat proximal tubular segment (PTS) system. An equal mixture of Fe2+/Fe3+ (4 mM total), when added to PTS, caused marked cytotoxicity [as defined by lactate dehydrogenase (LDH) release] and lipid peroxidation [assessed by malondialdehyde (MDA) increments]. Fe2+ or Fe3+ alone each induced massive MDA elevations, but only Fe2+ caused cytotoxicity. Although both DMTU and benzoate decreased LDH release during the Fe2+/Fe3+ challenge, mannitol and GSH did not, despite equivalent reductions in .OH (gauged by the salicylate trap method). GSH and catalase (but not DMTU, benzoate, or mannitol) decreased MDA concentrations, suggesting the Fe-driven lipid peroxidation was more H2O2 than .OH dependent. Deferoxamine totally blocked Fe-induced LDH release, even under conditions in which it caused an apparent increase in .OH generation. Mgb paradoxically protected against Fe-mediated PTS injury, an effect largely reproduced by albumin. In conclusion, these data suggest that: (a) Fe can cause PTS lipid peroxidation and cytotoxicity by a non-.OH-dependent mechanism; (b) Fe-mediated cytotoxicity and lipid peroxidation are not necessarily linked; and (c) Mgb paradoxically protects PTS against Fe-mediated injury, suggesting that: (i) Mgb Fe may require liberation from its porphyrin ring before exerting toxicity; and (ii) the protein residue may blunt the resulting injury.
Synthesis of Collagen Is Dysregulated in Cultured Fibroblasts Derived From Skin of Subjects With Varicose Veins as It Is in Venous Smooth Muscle Cells
Authors: Patricia Sansilvestri-Morel, Alain Rupin, Stéphane Jaisson, Jean-Noël Fabiani, Tony J. Verbeuren, Paul M. Vanhoutte
Journal: Circulation (2002)

Background — The dilatation and tortuosity observed in varicose veins provide evidence for progressive venous wall remodeling associated with abnormalities of smooth muscle cells and extracellular matrix. The present study was designed to examine if the phenotypic modulations observed in the venous smooth muscle cells of patients with varicose veins were also present in their dermal fibroblasts. Methods and Results — Collagen type I (collagen I), type III (collagen III), and type V (collagen V) were compared in dermal fibroblasts derived from the skin of control subjects and patients with varicose veins. The synthesis of collagen I, the release of its metabolites, and the expression of its mRNA were increased in fibroblasts from patients with varicose veins, whereas the synthesis of collagen III was decreased but not correlated with a decrease in mRNA expression and in metabolite release. Matrix metalloproteinases (MMP1, 2, 7, 8, 9, and 13) and their inhibitors (TIMP1 and 2) were quantified in both cell types; only the production of proMMP2 was increased in cells derived from patients with varicose veins. Conclusions — These findings suggest that the synthesis of collagen I and III is dysregulated in dermal fibroblasts derived from patients with varicose veins. These results are comparable with those observed in smooth muscle cells derived from varicose veins, thus suggesting a systemic alteration of tissue remodeling in subjects with varicose veins.
Serotonin, a Neurotransmitter Involved in the Regulation of Luteinizing Hormone Release*
Authors: MARIA L. VITALE, SARA R. CHIOCCHIO
Journal: Endocrine Reviews (1993)

FOLLOWING the discovery of various neurotransmitters in the brain, neuroendocrinologists have been challenged over the years with identifying those involved in the control of hormone secretion by the pituitary gland. A decade ago, Weiner and Ganong (1) and Kalra and Kalra (2) reviewed the role of serotonin (5-HT), among other neurotransmitters, in the release of luteinizing hormone (LH). This early literature was filled with conflict and controversy. As technology became more sophisticated and especially as immunohistochemistry and neurochemistry developed, it was possible to correlate physiological and experimental changes in LH secretion with changes in 5-HT metabolism in specific, discrete neuroanatomical areas. Nevertheless, at present, the physiological role of 5-HT in the control of LH secretion is still a matter of debate. The present review has been written in an effort to clarify the confusion resulting from the comparison of data from incompatible experimental designs. According to this, the information available on the participation of 5-HT in LH secretion was classified and discussed on the basis of the different experimental and physiological models.
American Joint Committee on Cancer Classification Predicts Outcome of Patients with Lacrimal Gland Adenoid Cystic Carcinoma
Authors: S. Mehdi Ahmad, Bita Esmaeli, Michelle Williams, John Nguyen, Aaron Fay, John Woog, Deepan Selvadurai, Jack Rootman, Ezekiel Weis, Dinesh Selva, Alan McNab, Dan DeAngelis, Alberto Calle, Adriana Lopez
Journal: Ophthalmology (2009)
Hypertension Prevalence, Awareness, Treatment, and Control in an Adult Type 1 Diabetes Population and a Comparable General Population
Authors: David M. Maahs, Gregory L. Kinney, Paul Wadwa, Janet K. Snell-Bergeon, Dana Dabelea, John Hokanson, James Ehrlich, Satish Garg, Robert H. Eckel, Marian J. Rewers
Journal: Diabetes Care (2005)

OBJECTIVE—To compare the prevalence, awareness, treatment, and control of hypertension in a population-representative sample of adults with type 1 diabetes and comparable nondiabetic control subjects. RESEARCH DESIGN AND METHODS—In 2000–2002, the Coronary Artery Calcification in Type 1 Diabetes Study enrolled 1,416 individuals aged 19–56 years with no known history of coronary artery disease: 652 type 1 diabetic patients (46% male, mean age 37 years) and 764 nondiabetic control subjects (50% male, mean age 39 years). Subjects were asked if they had been told by a physician that they had hypertension or were on a blood pressure medication. Blood pressure was measured using standardized Joint National Committee (JNC) protocol. RESULTS—Type 1 diabetic subjects, compared with nondiabetic subjects, had higher rates of hypertension prevalence (43 vs. 15%, P &amp;lt; 0.001), awareness (53 vs. 45%, P = 0.11), treatment (87 vs. 47%, P &amp;lt; 0.001), and control (55 vs. 32%, P &amp;lt; 0.001) for the JNC 6 goal (130/85 mmHg). Only 42% of all type 1 diabetic hypertensive subjects met the new JNC 7 goal (130/80 mmHg). Type 1 diabetic subjects had better blood pressure control (72 vs. 32%, P &amp;lt; 0.0001), using 140/90 mmHg as a common measure. The majority of treated subjects were on a single antihypertensive agent (75 vs. 64%). CONCLUSIONS—Subjects with type 1 diabetes have higher rates of hypertension prevalence, treatment, and control than nondiabetic subjects. However, hypertension remains largely uncontrolled, even if treated in high-risk populations, such as type 1 diabetic subjects and undiagnosed individuals in the general population. Achieving more stringent blood pressure goals will require increased attention and may necessitate the use of multiple antihypertensive agents.
Amoebic liver abscess draining into the bile ducts
Authors: R. L. Viana
Journal: Gut (1966)

The author describes the drainage of two amoebic abscesses into the biliary tract.This can be demonstrated radiologically and perhaps would be a worthwhile investigation in patients with hepatic abscesses as it might avoid surgical exploration or multiple aspirations.According to reports in the literature the spon- taneous drainage of an amoebic abscess of the liver into the biliary tree is a very rare event (Bowers and Barnes, 1960; Boquien and Lenne, 1962; Craig, 1934), and it may account for the rapid and com- plete recovery in a few cases within a few hours of starting anti-amoebic therapy.In this paper we describe two such cases. CASE HISTORIES
β-Blockers improve outcomes in kidney disease patients having noncardiac vascular surgery
Authors: G.M.J.M. Welten, M. Chonchol, S.E. Hoeks, O. Schouten, J.J. Bax, M. Dunkelgrün, Y.R.B.M. van Gestel, H.H.H. Feringa, R.T. van Domburg, D. Poldermans
Journal: Kidney International (2007)
A Case of Fulminant Type 1 Diabetes With Elevated Rheumatoid Factor and the Temporal Presence of Thyroid-Stimulating Hormone Receptor Antibody
Authors: Shinji Sakaue, Megumi Nagata, Osamu Wakabayashi, Toshiro Honda, Haruhiko Yoshimura, Etsuro Yamaguchi, Masaharu Nishimura
Journal: Diabetes Care (2002)

Type 1 diabetes is divided into two subtypes: autoimmune and idiopathic diabetes (1). Recently, fulminant type 1 diabetes was identified as a novel subtype of idiopathic diabetes (2). Imagawa et al. (2), who first identified this subtype, hypothesized that the disorder is caused by nonautoimmune mechanisms, including viral infection of exocrine pancreatic tissue. This hypothesis was generated from the negative test results for diabetes-related antibodies in patients with fulminant type 1 diabetes.

Additional pieces of supporting evidence were the absence of hyperexpression of major histocompatibility complex class I molecules in islets and the presence of lymphocyte infiltration in exocrine pancreatic tissue without insulitis in …
Abnormalities of the Central Visual Pathways Contributing to Traffic Accidents
Authors: Ella Freytag
Journal: JAMA (1968)

The autopsies of two automobile drivers and five pedestrians injured in traffic accidents revealed lesions in various parts of the central visual pathways which must have produced visual defects prior to the accidents. The manner in which the accidents took place suggested that the visual deficiencies of the victims may have caused or contributed to the accident. This information is significant for forensic purposes and for accident prevention.
Influence of Caffeine and other Methylxanthines on Mechanical Properties of Isolated Mammalian Heart Muscle: EVIDENCE FOR A DUAL MECHANISM OF ACTION
Authors: JOHN R. BLINKS, CAMILLE B. OLSON, BRIAN R. JEWELL, PAVEL BRAVENý
Journal: Circulation Research (1972)

Caffeine, theophylline, and theobromine have similar effects on the contractions of kitten atrial and papillary muscle preparations in vitro. In concentrations between 2 and 20 mM they both intensify and prolong the active state, as indicated by isometric and delayed-release isotonic contractions; contracture is not normally produced. Instantaneous force-velocity curves are shifted approximately symmetrically by caffeine; force-velocity curves derived from simple afterloaded contractions are misleading because of the great prolongation of activity. After the addition of caffeine the onset of the increased degree of activation is more rapid than that of the prolongation of activity; procaine antagonizes the prolongation of activity but not the intensification. In the presence of the methylxanthines, the duration of contraction is no longer abbreviated by isoproterenol, though it is still readily influenced by changes in frequency. The prolongation of activity by Sr 2^plus; differs in significant respects from that induced by methylxanthines. The results suggest that the methylxanthines exert two effects on excitation-contraction coupling. One of these is presumed to be the inhibition of calcium sequestration by the sarcoplasmic reticulum; the other may be an effect on the cell membrane that leads to increased calcium entry. Most of the features of the altered mechanical response can be explained on this basis if it is assumed that intracellular calcium stores available for release are depleted as a result of the process that impairs calcium sequestration.
Monophasic action potentials at discontinuation of cardiopulmonary bypass: evidence for contraction-excitation feedback in man.
Authors: P Taggart, P M Sutton, T Treasure, M Lab, W O'Brien, M Runnalls, R H Swanton, R W Emanuel
Journal: Circulation (1988)

Mechanical dysfunction is the strongest predictor of sudden cardiac death due to arrhythmia. Contraction-excitation feedback whereby changes in myocardial length/tension influence the time course of repolarization and excitability would provide a possible mechanism. Such a relationship has been shown in animals but has yet to be demonstrated in man. A useful model for studying this relationship is provided by the process of weaning off cardiopulmonary bypass after routine coronary artery surgery. During this weaning period of approximately 1 min, the heart is converted from being partially empty and flaccid (i.e., a "nonworking" state) to being filled and stretched to support the circulation (i.e., a "working" state). Monophasic action potentials (MAPs) were recorded from the left ventricular epicardium as a measure of repolarization time in 16 patients at discontinuation of cardiopulmonary bypass. Systolic pressure was recorded from the radial artery line. Measurements were made at three stages that related to different dynamic states of the heart: (1) starting to come off bypass ("minimally working"), defined as the time of first appearance of an inflection on the arterial pressure trace indicating the start of left ventricular ejection and valve opening, when arterial pressures represent left ventricular pressure, (2) half off bypass ("partially working"), and (3) off bypass ("wholly working"). During the process of discontinuing bypass MAP duration shortened, while systolic pressure increased. MAP duration at 90% and 60% repolarization (MAP D90, MAP D60) decreased from 288.0 +/- 29.5 msec (mean +/- SEM) and 235.0 +/- 27.9 msec in the minimally working heart to 274.5 +/- 30.2 msec and 224.2 +/- 27.3 msec in the partially working heart (p less than .001), with a subsequent decrease to 261.0 +/- 28.8 and 214.0 +/- 28.7 when the heart was wholly working (p less than .001). Systolic pressure increased from 54.1 +/- 9.3 mm Hg in the minimally working heart to 65.9 +/- 13.8 mm Hg in the partially working heart (p less than .001) and subsequently increased to 75.5 +/- 13.3 mm Hg when the heart was wholly working (p less than .001). Mean heart rates did not change significantly. A strong correlation was obtained between absolute MAP duration and systolic pressure. Regression analysis revealed: MAP D90 vs systolic pressure (p less than .001) and MAP D60 vs systolic pressure (p less than .01).(ABSTRACT TRUNCATED AT 400 WORDS)
STENOSING TENDOVAGINITIS AT THE RADIAL STYLOID: A BRIEF REVIEW OF SOME OF THE LITERATURE WITH REPORT OF A CASE
Authors: W. M. Brown
Journal: BMJ (1935)

protein 101 grams, and fat 158 grams.I increased the carbohydrate by ten grams.The next consultation was May, 1930, when a further increase in diet was prescribed.At the next consultation, on June 24th, 1935, I realized that this patient had at no time had symptoms of diabetes mellitus, and my notes told me that the diagnosis rested
Ras Antagonist Farnesylthiosalicylic Acid (FTS) Reduces Glomerular Cellular Proliferation and Macrophage Number in Rat Thy-1 Nephritis
Authors: Helen C. Clarke, Hemant M. Kocher, Arif Khwaja, Yoel Kloog, H. Terence Cook, Bruce M. Hendry
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Targeting the Ras family of monomeric GTPases has been suggested as a therapeutic strategy in proliferative renal diseases. This article reports the effects of Ras antagonist farnesylthiosalicylic acid (FTS) in rat thy-1 nephritis, a model in which cytokine-driven glomerular cell proliferation and invasion is likely to involve Ras signaling pathways. FTS in vitro specifically inhibits the binding of Ras to discrete membrane sites, thereby downregulating several Ras-dependent signaling functions and accelerating Ras degradation. Forty-four Lewis rats were given nephritis by day zero injection of a monoclonal thy-1 antibody ER4 (2.5mg/kg body wt). Twenty-two rats were then treated with daily intraperitoneal injection of FTS (5 mg/kg body wt) until sacrifice, and the remaining control rats were given vehicle alone (C). Six rats from each group were sacrificed at day 1 to establish equal injury; other sacrifice points were day 7 and day 10. Bromo-deoxyuridine (BrdU) was injected 1 h before sacrifice, after which sections were used for immunohistochemistry, which included detection of Ras expression, BrdU+ cells and macrophages/monocytes (ED1+). Thy-1 nephritis was associated with an increase in glomerular expression of Ki-Ras and N-Ras isoforms, which was almost fully prevented by FTS. FTS treatment was associated with: (a) a 54% reduction in the mean number of BrdU+ cells per glomerulus (P < 0.01), (b) a 50% reduction in macrophages/monocytes (ED1+) per glomerulus (P < 0.01), and (c) a reduction in 24-h proteinuria at day 10 (P < 0.05). These results show that Ras inhibition can reduce both glomerular cell proliferation and glomerular macrophage cell number in the thy-1 model and justify further study of FTS as a potential therapeutic in proliferative nephritis. E-mail: [email protected]
Chlamydia Infection and Lymphomas: Association Beyond Ocular Adnexal Lymphomas Highlighted by Multiple Detection Methods
Authors: Maurilio Ponzoni, Andrés J.M. Ferreri, Massimo Guidoboni, Antonia A. Lettini, Maria Giulia Cangi, Elisa Pasini, Luciano Sacchi, Lorenza Pecciarini, Stefano Grassi, Elena Dal Cin, Rosalba Stefano, Simone Magnino, Riccardo Dolcetti, Claudio Doglioni
Journal: Clinical Cancer Research (2008)

Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamydia detection tools to identify Cp elementary bodies-containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas.TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened by TETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls.Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/macrophages were the Cp carriers; electron microscopy showed the presence of intact Cp elementary bodies into these cells. Immunohistochemistry and TETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring.This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated.
Side effects of carbenoxolone sodium: a study of ambulant therapy of gastric ulcer.
Authors: R D Montgomery
Journal: Gut (1967)

EDITORIAL COMMENT Using 50 mg.three times a day, carbenoxolone sodium was found to be safe from side effects in normotensive patients without cardiac, renal, or hepatic disease.Hypertension, oedema, or serious potassium loss has been reported in up to 50 % of patients receiving carbenoxolone sodium, 300 mg.daily, for the treatment of gastric ulcer (Doll, Hill, Hutton, and Underwood, 1962; Doll, Hill, and Hutton, 1965; Turpie and Thomson, 1965; Horwich and Galloway, 1965).According to Turpie and Thomson's observa- tions on 10 patients, these side effects can also occur with a dosage of 150 mg.daily for four weeks, and they concluded that carbenoxolone sodium should only be used when close clinical supervision and biochemical facilities are available.This paper reports the effects on 50 out-patients treated with carbenoxolone sodium, 150 mg.daily for six weeks, as part of a long-term prospective study of the medical management of gastric ulcers based on this drug.
Measurements from light and polarised light microscopy of human coronary arteries fixed at distending pressure
Authors: P. B CANHAM, H. M FINLAY, J. G DIXON, D. R BOUGHNER, A. CHEN
Journal: Cardiovascular Research (1989)

With the long term goal of improving our understanding of the mechanisms involved in coronary artery spasm, we have undertaken a two part study of the artery structure. We have made a comparison of the relative proportions of the different layers in proximal and distal regions of the main coronary arteries, and have quantitatively assessed their three dimensional structural fabric. Major coronary arteries from nine hearts were prepared for histological examination after fixation at a transmural pressure of 120 mm Hg. Measurements from 14 proximal and distal pairs of the cross sectioned arteries showed a dominant subendothelial layer, which diminished in thickness distally, with a small fraction of muscle cells interspersed with collagen. Three dimensional orientation measurements of the collagen and muscle components, which are birefringent, were obtained from one pair of segments from each of the left anterior descending, circumflex and right coronary arteries, using the polarising light microscope and Universal stage. Findings showed (1) a single circumferential order of adventitial collagen, with a mean circular standard deviation (CSD) of 22.3°; (2) very highly ordered medial smooth muscle, mean CSD of 5.0° (both findings are quantitatively similar between proximal and distal segments of artery, and between arteries); and (3) a multilayered fabric of collagen in the subendothelium in all vessel segments. The principal contributor to functional differences between proximal and distal regions may be the prominent and structurally varied subendothelial layer of the coronary arteries.
Favorable association between genetic polymorphisms near the IL28B gene and hepatic steatosis: Direct or indirect?
Authors: Hidenori Toyoda, Takashi Kumada
Journal: Journal of Hepatology (2012)

and the single nucleotide polymorphisms: a milestone to tailor-made therapy for chronic hepatitis C. Hepatol Res 2010;40:449–460. Hidenori Toyoda⇑ Takashi Kumada Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu 503-8502, Japan ⇑ Corresponding author. Tel.: +81 584 81 3341; fax: +81 584 75 5715. E-mail address: hmtoyoda@spice.ocn.ne.jp (H. Toyoda). JOURNAL OF HEPATOLOGY