tbuckley/cabot-search huggingface dataset:
Use of Multiple Photosensitizers and Wavelengths During Photodynamic Therapy: A New Approach To Enhance Tumor Eradication
Authors: J. S. Nelson, L.-H. L. Liaw, R. A. Lahlum, P. L. Cooper, M. W. Berns
Journal: JNCI Journal of the National Cancer Institute (1990)

Several studies have examined the synergism of hyperthermia or chemotherapy agents in combination with photodynamic therapy (PDT) to enhance tumor eradication. In our unique approach to treatment, multiple photosensitizers and wavelengths were used: two photosensitizers, Photofrin II and meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4), irradiated at the appropriate therapeutic wavelength for each photosensitizer. EMT-6 mammary tumors were induced in the flanks of BALB/c mice. The mice were assigned to a control group (50 mice) or treatment group (150 mice). All treatment animals and some control animals received photosensitizing drug (5 mg/kg of TPPS4, 5 mg/kg of Photofrin II, or 2.5 mg/kg of both TPPS4 and Photofrin II). All treatment animals and some control animals also received light treatment (630 nm for TPPS4 and/or 658 nm for Photofrin II). The results show that the approach using both drugs and the corresponding therapeutic wavelengths enhanced the effectiveness of PDT. This approach achieved a cure rate of up to 100%, which was, depending on the light intensity used, as much as 40% greater than the rate achieved by the approach using one drug and one wavelength. The results also show that lesser amounts of drug and/or light may be required if both drugs and wavelengths are used, thus lowering the chances of side effects common to PDT. Furthermore, the results indicate that the increased tumor kill is due to a synergistic effect of the two photosensitizers that was tested on the tumor microvasculature in the first few hours after PDT.
Ranibizumab for Macular Edema following Central Retinal Vein Occlusion
Authors: David M. Brown, Peter A. Campochiaro, Rishi P. Singh, Zhengrong Li, Sarah Gray, Namrata Saroj, Amy Chen Rundle, Roman G. Rubio, Wendy Yee Murahashi
Journal: Ophthalmology (2010)
Bullying in schools
Authors: V. Rao
Journal: BMJ (1995)

BronchioliisHome observation is inadvisable EDIrOR,-David Isaacs's editorial on bronchiolitis contains guidelines that should cause some concern.Bronchiolitis does not always fit into the static categories of mild, moderate, or severe but can carry an infant through to an obtunded state relatively quickly.Thus the suggestion that babies with moderate disease with a respiratory rate of up to 70 can be observed at home is worrying.It is also of concern that pulse oximetry should be con- sidered to be relevant outside hospital.If the problem is indeed in the airways and not an interstitial lung problem then oxygen saturation should remain normal until the point at which respiratory muscle fatigue occurs.Other clinical observations in association with an increasing tachypnoea, such as heart rate and level of respon- siveness, should predict this event before decom- pensation occurs.At this point a child needs not only supplementary oxygen but ventilatory support, and the logistics of providing this outside hospital hardly makes this a safe option.
One Billion Years of bZIP Transcription Factor Evolution: Conservation and Change in Dimerization and DNA-Binding Site Specificity
Authors: G. Amoutzias, A. Veron, J Weiner, M Robinson-Rechavi, E Bornberg-Bauer, S. Oliver, D. Robertson
Journal: Molecular Biology and Evolution (2006)

The genomic era has revealed that the large repertoire of observed animal phenotypes is dependent on changes in the expression patterns of a finite number of genes, which are mediated by a plethora of transcription factors (TFs) with distinct specificities. The dimerization of TFs can also increase the complexity of a genetic regulatory network manifold, by combining a small number of monomers into dimers with distinct functions. Therefore, studying the evolution of these dimerizing TFs is vital for understanding how complexity increased during animal evolution. We focus on the second largest family of dimerizing TFs, the basic-region leucine zipper (bZIP), and infer when it expanded and how bZIP DNA-binding and dimerization functions evolved during the major phases of animal evolution. Specifically, we classify the metazoan bZIPs into 19 families and confirm the ancient nature of at least 13 of these families, predating the split of the cnidaria. We observe fixation of a core dimerization network in the last common ancestor of protostomes–deuterostomes. This was followed by an expansion of the number of proteins in the network, but no major dimerization changes in interaction partners, during the emergence of vertebrates. In conclusion, the bZIPs are an excellent model with which to understand how DNA binding and protein interactions of TFs evolved during animal evolution.
Differential Expression of Full-length Telomerase Reverse Transcriptase mRNA and Telomerase Activity between Normal and Malignant Renal Tissues
Authors: Yidong Fan, Zhaoxu Liu, Xiaolei Fang, Zheng Ge, Nan Ge, Yong Jia, Peng Sun, Fenglan Lou, Magnus Björkholm, Astrid Gruber, Peter Ekman, Dawei Xu
Journal: Clinical Cancer Research (2005)

Abstract Activation of telomerase, a key event during immortalization and malignant transformation, requires expression of the telomerase reverse transcriptase (hTERT). Consistently, lack of telomerase activity and hTERT expression occurs in most normal human somatic cells. However, it has been observed that both normal and cancerous renal tissues express hTERT whereas only the latter exhibits telomerase activity. The mechanism underlying the dissociation between hTERT expression and telomerase activity is unclear. In the present study, we examined telomerase activity and alternative splicing of hTERT transcripts in renal cell carcinoma (RCC) specimens and adjacent normal tissues from 33 patients with RCC. Telomerase activity was detectable in 27 of 33 (82%) RCC samples but none in their normal counterparts. Thirty-two of 33 tumors expressed overall hTERT mRNA and 27 of them contained full-length hTERT transcripts, all with telomerase activity. Although 42% (14 of 33) of normal renal samples expressed hTERT mRNA, none of them had full-length hTERT transcripts, coinciding with lack of telomerase activity. The presence of full-length hTERT mRNA and telomerase activity was significantly associated with c-MYC induction. In tumors, absence of full-length hTERT mRNA or telomerase activity defines a subgroup of nonmetastatic, early-stage RCCs. Taken together, telomerase repression in normal renal tissues is attributed to the absence of full-length hTERT transcripts, whereas telomerase activation is achieved via induction of or switch to expression of full-length hTERT mRNA during the oncogenic process of kidneys, and associated with aggressive RCCs.
Mycobacterial P1-Type ATPases Mediate Resistance to Zinc Poisoning in Human Macrophages
Authors: Hélène Botella, Pascale Peyron, Florence Levillain, Renaud Poincloux, Yannick Poquet, Irène Brandli, Chuan Wang, Ludovic Tailleux, Sylvain Tilleul, Guillaume M. Charrière, Simon J. Waddell, Maria Foti, Geanncarlo Lugo-Villarino, Qian Gao, Isabelle Maridonneau-Parini, Philip D. Butcher, Paola Ricciardi Castagnoli, Brigitte Gicquel, Chantal de Chastellier, Olivier Neyrolles
Journal: Cell Host & Microbe (2011)

Mycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning. In particular, mycobacterial genes encoding heavy metal efflux P-type ATPases CtpC, CtpG, and CtpV, and host cell metallothioneins and zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed a burst of free zinc inside macrophages, and intraphagosomal zinc accumulation within a few hours postinfection. Zinc exposure led to rapid CtpC induction, and ctpC deficiency caused zinc retention within the mycobacterial cytoplasm, leading to impaired intracellular growth of the bacilli. Thus, the use of P(1)-type ATPases represents a M. tuberculosis strategy to neutralize the toxic effects of zinc in macrophages. We propose that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race.
Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea
Authors: J. M. Beecroft, V. Hoffstein, A. Pierratos, C. T. Chan, P. A. McFarlane, P. J. Hanly
Journal: European Respiratory Journal (2007)

Sleep apnoea is common in patients with end-stage renal disease (ESRD). It was hypothesised that this is related to a narrower upper airway. Upper airway dimensions in patients with and without ESRD and sleep apnoea were compared, in order to determine whether upper airway changes associated with ESRD could contribute to the development of sleep apnoea. An acoustic reflection technique was used to estimate pharyngeal cross-sectional area. Sleep apnoea was assessed by overnight polysomnography. A total of 44 patients with ESRD receiving conventional haemodialysis and 41 subjects with normal renal function were studied. ESRD and control groups were further categorised by the presence or absence of sleep apnoea (apnoea/hypopnoea index > or =10 events.h(-1)). The pharyngeal area was smaller in patients with ESRD compared with subjects with normal renal function: 3.04 +/- 0.84 versus 3.46 +/- 0.80 cm(2) for the functional residual capacity and 1.99 +/- 0.51 versus 2.14 +/- 0.58 cm(2) for the residual volume. The pharynx is narrower in patients with ESRD than in subjects with normal renal function. In conclusion, since a narrower upper airway predisposes to upper airway occlusion during sleep, it is suggested that this factor contributes to the pathogenesis of sleep apnoea in dialysis-dependent patients.
Investigation of young children with severe recurrent wheeze: any clinical benefit?
Authors: S. Saglani
Journal: European Respiratory Journal (2005)

The management of young children with severe recurrent wheeze is difficult because symptoms are often refractory to conventional asthma therapy and other diagnoses must be excluded. The present authors aimed to evaluate the outcome of detailed, invasive investigations in such patients. Children aged between 3 months and 5 yrs with severe recurrent wheezing, who had been referred to a tertiary centre, underwent a protocol of investigations including a chest computed tomography scan, blood tests, nasal ciliary brushings, fibreoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial biopsy and passage of an oesophageal pH probe. A total of 47 children (25 males) with a median age of 26 (range 5-58) months underwent investigation. Of these, 39% were atopic, two-thirds had evidence of gastro-oesophageal reflux and 37 out of 47 had an abnormal bronchoscopy. Findings included structural abnormalities (13 out of 37), excessive mucus (20 out of 37) and macroscopic inflammation (10 out of 37). BAL revealed bacterial growth in 12 out of 44 (27%) patients. Good quality endobronchial biopsies were obtained from 36 out of 46 (78%) patients; of these, 44% had tissue eosinophilia and 28% had a thickened reticular basement membrane. Additional investigations (including bronchoscopy) in young children with severe wheeze may help to identify positive diagnoses and provide information to support a clinical diagnosis of asthma. This hypothesis-generating work should form the basis of future interventional studies.
White Matter Lesions Detected by Magnetic Resonance Imaging After Radiotherapy and High-Dose Chemotherapy in Children With Medulloblastoma or Primitive Neuroectodermal Tumor
Authors: Maryam Fouladi, Murali Chintagumpala, Fred H. Laningham, David Ashley, Stewart J. Kellie, James W. Langston, Charles W. McCluggage, Shaio Woo, Mehmet Kocak, Kevin Krull, Larry E. Kun, Raymond K. Mulhern, Amar Gajjar
Journal: Journal of Clinical Oncology (2004)

Purpose White matter lesions (WMLs) have been described as a delayed effect of cranial irradiation in children with brain tumors, or a transient subacute effect characterized by an intralesional or perilesional reaction. We report the occurrence of subacute WMLs detected by magnetic resonance imaging (MRI) in children treated for medulloblastoma or primitive neuroectodermal tumor (PNET) and document the associated clinical, radiologic, and neurocognitive findings. Patients and Methods Among 134 patients with medulloblastoma or supratentorial PNET treated prospectively with risk-adjusted craniospinal irradiation and conformal boost to the tumor bed, followed by four high-dose chemotherapy (HDC) cycles with stem-cell rescue, 22 developed WMLs on T1-weighted imaging with and without contrast and/or T2-weighted imaging on MRI. Patients had ≥ 12 months of follow-up. Neurocognitive assessments included intelligence quotient (IQ) tests and tests of academic achievement. Results Twenty-two patients developed WMLs at a median of 7.8 months after starting therapy (range, 1.9 to 13.0 months). Lesions were predominantly in the pons (n = 8) and cerebellum (n = 6). Sixteen patients (73%) had WML resolution at a median of 6.2 months (range, 1.68 to 23.5 months) after onset; two patients developed necrosis and atrophy. Three developed persistent neurologic deficits. Cumulative incidence of WMLs at 1 year was 15% ± 3%. Patients with WMLs had a significant decline in estimated IQ (−2.5 per year; P = .03) and math (−4.5 per year; P = .003) scores. Conclusion WMLs in medulloblastoma or PNET patients treated with conformal radiotherapy and HDC are typically transient and asymptomatic, and may mimic early tumor recurrence. A minority of patients with WMLs develop permanent neurologic deficits and imaging changes. Overall, the presence of WMLs is associated with greater neurocognitive decline.
HYPERTENSION IN THE ELDERLY
Authors: Norman M. Kaplan, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract Elderly people have a very high prevalence of hypertension, which markedly increases their risk for cardiovascular morbidity and mortality. Convincing evidence demonstrates the effectiveness of antihypertensive therapy in reducing these risks significantly. With appropriate caution, most elderly hypertensives can be treated and thereby protected from many of the debilities of old age.
Pooled Results From 38 Analyses of the Accuracy of Distress Thermometer and Other Ultra-Short Methods of Detecting Cancer-Related Mood Disorders
Authors: Alex J. Mitchell
Journal: Journal of Clinical Oncology (2007)

Ultra-short screening tools involving fewer than five questions have been recommended as a simple method of detecting distress, anxiety, or depression in cancer settings. Such methods have practical appeal, but their diagnostic accuracy is unclear. A literature search limited to diagnostic validity studies of ultra-short screening in cancer settings identified 38 analyses, including 19 assessing the Distress Thermometer alone, involving a total of 6,414 unique patients. The pooled ability of ultra-short methods to detect depression was given by a sensitivity of 78.4%, a specificity of 66.8%, a positive predictive value (PPV) of 34.2%, and a negative predictive value (NPV) of 93.4%. Thus these tools were very good at excluding possible cases of depression but poor at confirming a suspected diagnosis. The pooled ability of ultra-short methods to detect anxiety was given by a sensitivity of 77.3% and a specificity of 56.6% (PPV, 55.2%; NPV, 80.25%) and for distress a sensitivity of 78.3% and a specificity of 66.5% (PPV, 59.7%; NPV, of 82.8%). Results using the Distress Thermometer alone were similar. Scores of integrated accuracy, using the Youden index and diagnostic odds ratio, suggested modest overall accuracy with least success in diagnosing anxiety disorders. Ultra-short methods were modestly effective in screening for mood disorders. Their rule-in ability was poorer than their rule-out ability. Ultra-short methods cannot be used alone to diagnose depression, anxiety, or distress in cancer patients but they may be considered as a first-stage screen to rule out cases of depression.
Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects
Authors: Brigitte Bauvois, Daniel Dauzonne
Journal: Medicinal Research Reviews (2005)

Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti-cancer and anti-inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity.
Pathogenesis and Epidemiology of Chronic Pancreatitis
Authors: H Sarles, J P Bernard, C Johnson
Journal: Annual Review of Medicine (1989)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations
Authors: Lisa M. Schimanski, Hal Drakesmith, Alison T. Merryweather-Clarke, Vip Viprakasit, Jon P. Edwards, Emma Sweetland, Judy M. Bastin, Diana Cowley, Yingyong Chinthammitr, Kathryn J. H. Robson, Alain R. M. Townsend
Journal: Blood (2005)
Human cholesterol 7α-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype
Authors: Clive R. Pullinger, Celeste Eng, Gerald Salen, Sarah Shefer, Ashok K. Batta, Sandra K. Erickson, Andrea Verhagen, Christopher R. Rivera, Sean J. Mulvihill, Mary J. Malloy, John P. Kane
Journal: Journal of Clinical Investigation (2002)

Bile acid synthesis plays a critical role in the maintenance of mammalian cholesterol homeostasis. The CYP7A1 gene encodes the enzyme cholesterol 7alpha-hydroxylase, which catalyzes the initial step in cholesterol catabolism and bile acid synthesis. We report here a new metabolic disorder presenting with hyperlipidemia caused by a homozygous deletion mutation in CYP7A1. The mutation leads to a frameshift (L413fsX414) that results in loss of the active site and enzyme function. High levels of LDL cholesterol were seen in three homozygous subjects. Analysis of a liver biopsy and stool from one of these subjects revealed double the normal hepatic cholesterol content, a markedly deficient rate of bile acid excretion, and evidence for upregulation of the alternative bile acid pathway. Two male subjects studied had hypertriglyceridemia and premature gallstone disease, and their LDL cholesterol levels were noticeably resistant to 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. One subject also had premature coronary and peripheral vascular disease. Study of the kindred, which is of English and Celtic background, revealed that individuals heterozygous for the mutation are also hyperlipidemic, indicating that this is a codominant disorder.
The Significance of Lung Function Changes in Asbestosis
Authors: R. Williams, P. Hugh-Jones
Journal: Thorax (1960)

Asbestos isthenamegivento a series of minerals composedof fibroussilicates of magnesium andironwhichfindwidespread usein industry. Inhalation of thedustmay cause asbestosis, acrippling formofpulmonary fibrosis, whichusually doesnotappearuntil manyyears aftertheinitial exposure. Thereisalsoan increased incidence ofcarcinoma ofthelungin patients withasbestosis, andDoll(1955) estimated thattheriskoflungcancerinasbestos workers wasapproximately 10timesgreater thaninthe general population. Thediagnosis ofasbestosis atpresent depends onthehistory ofexposure tothedusttogether withcertain physical signsand radiological changes. Themostcharacteristic features ofthe latter areaground-glass mottling ofthelower zonesofthelungfields witha shaggy border to theheart. Thephysical signs areclubbing ofthe fingers andfinemetallic crepitations onauscultation ofthelungbases. Unfortunately manycases evenwithdefinite physical signs donotshowthe characteristic radiological changes, andtheearly diagnosis ofthedisease may bemostdifficult. The presence of 'asbestosis bodies inthe sputumsimply provesthatasbestos dusthas beeninhaled anddoesnotnecessarily imply that fibrosis ispresent. Thepurpose ofthepresent workwastorelate thechanges inlungfunction inasbestosis tothe clinical andradiological signs ofthedisease and totryanddetermine thevalue oflungfunction tests inassisting withitsearly diagnosis. PREviousLUNG FUNCTIONSTUDIES
Myofilament Calcium Sensitivity in Skinned Rat Cardiac Trabeculae
Authors: John P. Konhilas, Thomas C. Irving, Pieter P. de Tombe
Journal: Circulation Research (2002)

The increase in myofilament Ca 2+ responsiveness on an increase in sarcomere length (SL) is, in part, the cellular basis for Frank-Starling’s law of the heart. It has been suggested that a decrease in myofilament lattice spacing (LS) in response to an increase in SL underlies this phenomenon. This hypothesis is supported by previous studies in which reduced muscle width induced by osmotic compression was associated with an increase in Ca 2+ sensitivity, mimicking those changes observed with an increase in SL. To evaluate this hypothesis, we directly measured LS by synchrotron x-ray diffraction as function of SL in skinned rat cardiac trabeculae bathed in 0% to 6% dextran solutions (MW 413 000). We found that EC 50 , [Ca 2+ ] at which force is half-maximal, at SL between 1.95 and 2.25 μm did not vary in proportion to LS when 3% or 6% dextran solutions were applied. We also found that moderate compression (1% dextran) of skinned trabeculae at SL=2.02 μm reduced LS (LS=42.29±0.14 nm) to match that of uncompressed fibers at a long SL (SL=2.19 μm; LS=42.28±0.15 nm). Whereas increasing SL from 2.02 to 2.19 μm significantly increased Ca 2+ sensitivity as indexed by the EC 50 parameter (2.87±0.11 μmol/L to 2.52±0.12 μmol/L), similar reduction in myofilament lattice spacing achieved by compression with 1% dextran did not alter Ca 2+ sensitivity (2.87±0.10 μmol/L) at the short SL. We conclude that alterations in myofilament lattice spacing may not be the mechanism that underlies the sarcomere length–induced alteration of calcium sensitivity in skinned myocardium.
Specific polymorphism groups within a PPARg-ABCA1 pathway are associated with future death or myocardial infarction in patients with angiographically documented coronary artery disease
Authors: Cory A. King, Joseph B. Muhlestein, Noal I. Hart, Jill B. Faatz, Henri O.F. Mulhuizen, Jeffrey L. Anderson, Bryant M. Whiting, Benjamin D. Home, John F. Carquist
Journal: Journal of the American College of Cardiology (2002)