tbuckley/cabot-search huggingface dataset:
Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas.
Authors: S Khosla, V M Patel, I D Hay, D J Schaid, C S Grant, J A van Heerden, S N Thibodeau
Journal: Journal of Clinical Investigation (1991)

Loss of heterozygosity (LOH) at specific loci may help localize tumor suppressor genes involved in the formation of various familial and sporadic tumors. In addition, the genetic loci for a number of familial tumor syndromes have been mapped by linkage analysis. To explore the possible role of tumor suppressor genes in endocrine tumors, we tested 41 pheochromocytomas (34 sporadic and 7 familial) and 11 medullary thyroid cancers (MTC) (10 sporadic and 1 familial) for LOH near a variety of potentially important genetic loci: (a) the multiple endocrine neoplasia type 2A (MEN 2A) locus on chromosome 10; (b) the von Hippel-Lindau locus on 3p; and (c) the p53 and neurofibromatosis 1 loci on 17. We also examined chromosomes 1p and 22q because previous studies in a small number of pheochromocytomas and MTCs suggested LOH in these regions. Background rates for LOH were assessed using several "random" probes. Finally, we examined a number of clinical and histologic characteristics of these tumors for possible correlations with specific genetic alterations. LOH in the region of the MEN 2A locus was uncommon (0% for MTCs, 5% for pheochromocytomas). However, we found significant allelic losses in pheochromocytomas on chromosomes 1p (42%), 3p (16%), 17p (24%), and 22q (31%). We also noted a correlation between LOH on 1p and urinary excretion of metanephrine by these patients (P = 0.02). LOH on 1p, 3p, and 17p also appeared to be associated with increased tumor volume. Analysis of the smaller number of MTCs demonstrated allelic losses on chromosomes 1p and 22q. Our results suggest that tumor formation and/or progression in pheochromocytomas and MTCs involves multiple genes, analogous with the model proposed for colon carcinoma.
Observations on the Value of some of the Methods used for Testing Disinfectants
Authors: E. Klein
Journal: BMJ (1904)

THE usual method of testing and comparing disinfectants consists in exposing for a given time cultures or emulsions of a particular microbe to dilutions of the disinfectant.This, no doubt, is of value in comparing with one another various dis- infectants or their dilutions, and although it affords a suffi- ciently reliable index of the efficacy and power of a given disinfectant in a definite dilution and for a definite time exposure, it cannot, for reasons to be mentioned presently, supply an absolute guide for the application of the disinfectant in actual practice.In practical lile a disinfectant is applied by a surgeon, by the sanitarian, or by the nurse, not to an artificial culture or to an emulsion of an artificial culture, but to materials, such as excretions, secretions, morbid products, and morbid tissues, derived directly or indirectly from the human or animal bodies.The microbes to be acted upon by the disinfectant are embedded in, surrounded by, and mixed with various materials.This condition cannot obviously be compared with that of a microbe in a broth culture, or with a watery or salt emulsion of the growth taken from an artificial culture.The surgeon who wishes to disinfect a wound and to keep it antiseptic, has to apply the disinfectant to tissues and not to a watery emulsion; the nurse who is supposed to dis- infect a typhoid stool with a given disinfectant is not acting on a watery or saline emulsion of a culture of the typlhoid bacillus, but on materials of a highly-complex composition, and altogether of a different nature from the laboratory
Efalizumab-induced hypertrichosis
Authors: E. Rallis, P. Tapinis, C.D. Verros
Journal: British Journal of Dermatology (2008)

Journal Article Efalizumab‐induced hypertrichosis Get access E. Rallis, E. Rallis Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar P. Tapinis, P. Tapinis Internal Medicine, Army General Hospital, 11 Pafsaniou St Athens 116 35, Greece Search for other works by this author on: Oxford Academic Google Scholar C.D. Verros C.D. Verros Private Practice, Tripolis, Greece E‐mail: efrall@otenet.gr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 5, 1 May 2008, Pages 1158–1159, https://doi.org/10.1111/j.1365-2133.2008.08511.x Published: 01 May 2008
Methylprednisolone in Spinal Cord Injuries
Authors: David H. Spodick
Journal: JAMA (1984)

<h3>To the Editor.—</h3> The double-blind randomized trial of low-<i>v</i>high-dose methylprednisolone in acute spinal cord injury was well conceived and executed (and should have been, perhaps, because it sports 20 authors!).<sup>1</sup>It also called for Dr Kobrine's<sup>2</sup>appropriate editorial. I wish to quibble only with Dr Kobrine's designation of "the next logical study, namely, a prospective randomized study comparing normal-steroid therapy with placebo treatment." Dr Kobrine is, of course, correct. However, one might equally conceive that randomized study as the<i>previous</i>"logical study," since, despite the long, inadequately validated use of corticosteroids in nervous system injuries, the appropriate (logical) step would have been to<i>begin</i>with a controlled, randomized trial.<sup>3</sup>Lacking that, the use of these powerful agents—at any dose—has left unresolved the possibility that some or all patients may have become worse because of this treatment. This possibility is, of course, always present with the
Changes in longevity and causes of death among persons with hemophilia A
Authors: Terence L. Chorba, Robert C. Holman, Tara W. Strine, Matthew J. Clarke, Bruce L. Evatt
Journal: American Journal of Hematology (1994)

To examine recent changes in longevity and the causes of death among persons with hemophilia A, we evaluated death certificate data for persons who died in the United States from 1968 through 1989 and had hemophilia A or congenital Factor VIII disorder (ICD code 286.0) listed on the death certificate as one of the multiple causes of death. Multiple-cause-of-death mortality data for the United States from 1968 to 1989 were examined to compare death rates by year, focusing on death rates and causes of death for 1979-1981, 1983-1985, and 1987-1989. Gender, age group, race, geographic region, and median age at death of persons with hemophilia A and human immunodeficiency virus (HIV)-related disease listed as a cause of death were compared with those with hemophilia A without HIV-related disease. From 1968 through 1989, 2,792 hemophilia A deaths were reported. The death rate increased from 0.5 to 1.3 per 1,000,000 persons. From 1979-1981 through 1987-1989, mortality increased in all age groups above 9 years of age and age at death shifted markedly to lower ages. Median age at death decreased from 57 years in 1979-1981 to 40 years in 1987-1989. The percentage of deaths due to hemorrhage or diseases of the circulatory system decreased markedly as the result of the increase in deaths associated with HIV infection or infections other than HIV infection. Spread of HIV-1 infection in persons with hemophilia A has disrupted the reduction in mortality seen with factor replacement therapy, implementation of home care, and use of comprehensive hemophilia treatment centers. It is hoped that advances in the care of HIV-infected persons will improve survival in the hemophilia community.
Tuberculous gumma following venepuncture
Authors: D. Vidal, M. Barnadas, M. Pérez, P. Coll, A. Alomar
Journal: British Journal of Dermatology (2001)

An 88‐year‐old man with a past medical history of pulmonary tuberculosis presented with a 2‐year history of an indolent enlarging ulcerated nodule on his left wrist following a venous blood test. Skin biopsy of the ulcer showed granulomas, Ziehl–Neelsen stain was negative, and cultures grew Mycobacterium tuberculosis. Underlying bone and joint disease was excluded, and the lesion healed completely with 6 months of standard antituberculous treatment. We review the literature on tuberculous gumma following an injury.
Effect of non-nicotine cigarettes and carbon monoxide on angina.
Authors: W S Aronow
Journal: Circulation (1980)

The effect of smoking five non-nicotine cigarettes and of breathing carbon monoxide on exercise-induced angina was evaluated in 12 patients with angina. Smoking increased venous carboxyhemoglobin from 1.71 to 5.35%, decreased exercise duration until angina 45%, increased ischemic ST-segment depression at angina from 1.33 to 1.52 mm, and decreased systolic blood pressure times heart rate at angina. Breathing carbon monoxide increased venous carboxyhemoglobin from 1.73 to 5.37%, decreased exercise duration until angina 35%, increased ischemic ST-segment depression at angina from 1.31 to 1.50 mm, and decreased systolic blood pressure times heart rate at angina. Greater decreases in exercise duration until angina and in systolic blood pressure times heart rate at angina (p less than 0.001) were observed after smoking than after breathing carbon monoxide. Tobacco components other than nicotine or carbon monoxide are responsible for a small decrease in exercise performance until angina.
A novel approach to port-wine stains
Authors: A. Ortiz
Journal: British Journal of Dermatology (2015)

ORIGINAL ARTICLE, p 669 Port‐wine stains (PWSs) are capillary vascular malformations that occur in 3 per 1000 live births. Selective photothermolysis of PWS blood vessels with the pulsed‐dye laser (PDL) is considered the gold standard of treatment. PDL is very effective at PWS clearance, with a low incidence of side‐effects.1 However, multiple treatments are required in part due to the body's normal wound healing response, which results in revascularization and regeneration of PWS blood vessels following laser exposure.2 PDL‐induced angiogenesis makes it very difficult to achieve complete clearance of PWSs. This has prompted investigation into combination therapy with antiangiogenic agents after laser irradiation to modulate the neovascularization skin response to laser damage and enhance the effects of laser therapy. Rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), was initially investigated as a potential adjuvant therapy after laser irradiation. Rapamycin is thought to have antiangiogenic properties through downregulation of hypoxia‐inducible factor (HIF)‐1α, which leads to a decrease in vascular endothelial growth factor (VEGF) production and reduction in the stimulation of VEGF by vascular endothelial cells.3 4 Both systemic and topical formulations of rapamycin have shown promising inhibition of neovascularization in the skin after laser treatment.5 6 Topical formulations are preferable in order to obviate systemic side‐effects, assuming that an appropriate depth of penetration is achievable. Initial studies with rapamycin have led to the investigation of other antiangiogenic agents such as imiquimod, which activates toll‐like receptor 7 leading to activation of antiangiogenic cytokines and reduction of angiogenic stimulators.7
New Multifunctional Molecular Conjugate Vector for Targeting, Imaging, and Therapy of Tumors
Authors: Elisabeth Garanger, Didier Boturyn, Zhaohui Jin, Pascal Dumy, Marie-Christine Favrot, Jean-Luc Coll
Journal: Molecular Therapy (2005)

We report the in vitro and in vivo characteristics of a new molecular conjugate vector for targeting and imaging of tumors. Its core is a cyclodecapeptide platform named RAFT, onto which two spatially independent functional domains can be covalently and stereospecifically linked: a cell-targeting domain for tumor targeting and a labeling domain able to carry two drugs and/or labeling agents. To prove the interest of this carrier, we used a well-known cRGD cyclopeptide, a ligand for the αvβ3 integrin. We demonstrate that this vector presenting four cRGD motifs very efficiently prevents αvβ3-mediated cell adhesion to vitronectin. Furthermore, it is actively endocytosed because of the multivalent cRGD presentation, a major advantage for drug delivery. In vivo experiments in nude mice reveal that repeated intratumoral injections of low doses of RAFT(cRGD)4 reduce tumor growth. Furthermore, RAFT(cRGD)4 significantly improves the targeting specificity of subcutaneous tumor masses as well as that of disseminated metastasis after intravenous injection. Thus, RAFT(cRGD)4 is specific, internalized, and perfectly controlled and can carry multiple biological functions on a single, spatially defined backbone, making it a powerful and versatile synthetic vector for drug delivery, molecular imaging, or both.
Abstract P1-02-07: Real-Time Functional Imaging of Tumor Vascular Normalization by Anti-Angiogenic Agents
Authors: HR Xing, Q Zhang, V Bindokas, J Shen, H Fan, RM. Hoffman
Journal: Cancer Research (2010)

Abstract Background: We describe here new technology that enables non-invasive imaging of normalization of tumor blood vessels by anti-angiogenic agents in real time. Materials and Methods: Variable-magnification in vivo-fluorescence imaging as well as fluorescence tomography were used to visualize vessel normalization. Results: Morphological changes in the same vessel prior to and after drug treatment were imaged with high resolution in real time. Differences in vascular responses to the mTOR inhibitor rapamycin and to an anti-VEGF antibody were functionally imaged. Tumor vessel normalization was demonstrated by significantly reduced leakiness and subsequent improved tumor delivery of Paclitaxel-BODPY as well as by normalized morphology. The tumor vascular pool agent, AngioSense750, was retained in tumors after both anti-VEGF antibody and rapamycin treatment as visualized by noninvasive fluorescence tomography. The anti-angiogenic therapy normalized vessels, which significantly enhanced the antitumor efficacy of Paclitaxel due to increased drug penetration throughout the tumor. Discussion: The optical imaging technology described here is thus a powerful real-tool imaging tool of functional and morphological tumor vessel normalization and its therapeutic consequences. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-07.
Engineering Human Tumor-specific Cytotoxic T Cells to Function in a Hypoxic Environment
Authors: Hongsung Kim, Guangyong Peng, John M Hicks, Heidi L Weiss, Erwin G Van Meir, Malcolm K Brenner, Patricia Yotnda
Journal: Molecular Therapy (2008)

Hypoxia occurs in many tumors and reduces the effectiveness of radio- and chemotherapy. Hypoxia also impedes immune responses to tumors, reducing T lymphocyte production of cytokines such as interleukin-2 (IL-2) and interferon gamma, as well as the survival and proliferation of these cells. We constructed a lentiviral vector encoding a bidirectional hypoxia-inducible responsive element (HRE) derived from human vascular endothelial growth factor, which drives the hIL-2 gene and a marker gene. We used a model of human B cell lymphoma to show that tumor-specific T cells modified with this vector upregulate hIL-2 expression when oxygen tension is low in vitro and in vivo. The consequence of this effect is to increase T-cell survival and proliferation whilst sustaining effector function, even in O(2) concentrations as low as 1%. The phenotype of the transduced cells is unchanged, as is their ability to migrate to tumor. HRE-IL-2-modified cytotoxic T lymphocytes (CTLs) produce faster and more complete tumor regression than parental CTLs and increase overall survival. Hypoxia-resistant T cells may thus be of value in the treatment of human tumors in which areas of hypoxia may otherwise account for resistance to this therapeutic strategy.
Ambulatory Electrocardiographic Monitoring
Authors: John S. Schroeder
Journal: JAMA (1976)

THE BREVITY of the standard 12-lead resting electrocardiogram (about 30 seconds) seriously limits its value in the detection of potentially lifethreatening cardiac arrhythmias or in estimating the effectiveness of antiarrhythmic therapy. Whereas a standard ECG records 50 to 100 cardiac cycles, the ambulatory ECG records over 100,000 cycles in one or two leads during an average 24-hour day. Not only does the ambulatory ECG provide a better overall estimate of a patient's arrhythmias, but it can detect problems that only occur at particular times of the day or in response to stress such as physical exertion or emotional excitement.<sup>1</sup> Current methods of obtaining and processing ambulatory ECG tape recordings and primary areas of clinical application using this technique will be described, based on more than five years' experience in the Cardiology Division at Stanford University Hospital. <h3>Technique</h3> Continuous ECG monitoring in an ambulatory patient requires a small portable tape
Tumor-Suppressive Functions of Leucine Zipper Transcription Factor–Like 1
Authors: Qun Wei, Wen Zhou, Weining Wang, Boning Gao, Linbo Wang, Jiang Cao, Zhi-Ping Liu
Journal: Cancer Research (2010)

Human leucine zipper transcription factor-like 1 (LZTFL1) is a novel gene with unknown biological functions. It is located in the chromosome region 3p21.3, a hotspot for tumor suppressor genes. To understand the biological functions of LZTFL1, we surveyed the expression level of LZTFL1 in tumor and normal samples in tissue microarrays and a clinical archive of 84 gastric cancer specimens using immunohistochemistry. We found that LZTFL1 is expressed highly in the epithelial cells of normal tissues and is significantly downregulated in the corresponding tumor samples. The expression level of LZTFL1 correlated significantly with the survival outcomes of the patients and had significant inverse correlation with tumor metastasis. Overexpression of LZTFL1 in tumor cells inhibited anchorage-independent cell growth and cell migration in vitro and repressed tumor growth in vivo. Furthermore, we show that LZTFL1 expression is upregulated on epithelial cell differentiation and is graded along the crypt-villus axis of the intestine, with weakest expression level in the proliferative zone of the crypt and highest expression level at the apex of the differentiation zone in the villus. Expression of LZTFL1 overlaps with that of E-cadherin at the plasma membrane. Our results indicate that LZTFL1 is a tumor suppressor and that loss of LZTFL1 expression has significant clinical outcomes. LZTFL1 expression may serve as an independent prognostic marker for survival outcome of gastric cancer patients. We propose that LZTFL1 may inhibit tumorigenesis by stabilizing E-cadherin-mediated adherens junction formation and promoting epithelial cell differentiation.
Infections of Intervertebral Disk
Authors: A. J. Bianco
Journal: JAMA (1963)

<h3>To the Editor:</h3> —Upon review of the six cases reported by Dr. O'Loughlin's group,<sup>1</sup>which incidentally appear to be identical to ours, I was surprised to find that only one of their six patients underwent biopsy, and the findings from this biopsy proved to be negative. Dr. O'Loughlin's statement that "no bacteriological or viral etiologic agents could be identified" does not, therefore, seem to be too surprising, at least to those investigators who appreciate the value of direct biopsy of a suspected infectious lesion to obtain material for bacteriologic culture and sensitivity studies. In commenting on Sherbel and Gardner's series, Dr. O'Loughlin et al state: "Vigorous diagnostic effort led to proof of infection either by aspiration or curettement of the intervertebral disk in 7 of the 10 cases with positive culture in each of these." To suggest, therefore, that our consecutive positive cultures for<i>Staphylococcus aureus</i>, obtained from five
CHARACTERIZATION OF SPLENIC LYMPHOID CELLS IN FETAL AND NEWBORN MICE
Authors: Patricia G. Spear, Ai-Lan Wang, Urs Rutishauser, Gerald M. Edelman
Journal: The Journal of Experimental Medicine (1973)

In order to clarify the cellular events that precede the onset of immunological competence in the mouse, we have characterized and quantitated the lymphoid cells of the spleen as a function of age. Our results show that T cells and B cells both appeared in the spleens of Swiss-L mice as early as the 15th-16th day of gestation. Antigen-binding cells specific for each of three different antigens were also first detected during this same 24 h interval. The B cells and three varieties of antigen-binding cells increased in number rapidly and in parallel until about 1 wk after birth. The T cells, which were more numerous than B cells at first, increased in number somewhat more slowly. Coincident with the onset of response to antigen, there was a further increase in B cell numbers and a decrease in the T cell to B cell ratio. The capacity to respond to antigen by cellular proliferation and synthesis of antibody did not arise until about 2 wk after birth although there were no quantitative changes in the total numbers of T cells, B cells, and antigen-binding cells between 1 and 2 wk of age. Some qualitative change, such as the functional maturation of an antigen-reactive cell, may be required during this interval for the onset of this immunological response. Although the numbers of antigen-binding cells present in fetuses and young animals were smaller than in adults, we have as yet been unable to detect any restriction in the variety of specificities that can be expressed in fetuses, either in the kinds of antigens bound or in the range of avidities with which a single antigen is bound.
Peak Oxygen Intake During Physical Fitness Program for Middle-Aged Men
Authors: John Naughton
Journal: JAMA (1965)

A group of presumably healthy, sedentary men participated in a physical fitness program for seven months. Their maximum oxygen intake was determined during either a standard treadmill test or an "all-out run" or both. Eighteen men tested on the treadmill before and after the test had an increase in their peak oxygen uptake from 31.3 to 36.8 ml/kg/min (<i>P</i>&lt;0.001). Ten of the subjects who were tested by both methods before and after seven months of training had statistically significant increases in their peak oxygen intakes. Their peak performance was consistently higher with the "all-out run" than it was on the treadmill. Eight men failed to increase their peak energy expenditure following training; four of these subjects were tested twice with the treadmill test and their peak performances remained the same before and after the program.
Computed tomography of the colon in elderly people
Authors: M Fink, A H Freeman, A K Dixon, N K Coni
Journal: BMJ (1994)

Barium enema has long been the standard imaging test for investigating the colon. It may, however, be unsuccessful in elderly people and is often poorly tolerated by patients and disliked by staff; frail patients often have to be admitted to hospital for it. A previous, pilot study suggested that computed tomography might be a satisfactory alternative.1 We report our experience of using computed tomography as the initial radiological examination to investigate possible disease of the colon in frail elderly people.

In 1992, 66 elderly patients (age range 70-93, mean 82) were referred for computed tomography of the colon. Fifty one were referred by geriatricians who had helped to develop this new diagnostic approach in our pilot study. Thirty two patients were already inpatients when investigated, and the rest were seen as outpatients.

In July 1993 the notes of these patients were …
Reply to ‘Absence of JAK-2 (Val617Phe) point mutations in multiple myeloma’ by Dr Qin Huang et al. referred to ‘Screening of JAK2 V617F mutation in multiple myeloma’ from Fiorini A et al. published in Leukemia 2006, October 20
Authors: A Fiorini, G Farina, G Reddiconto, M Palladino, E Rossi, T Za, L Laurenti, S Giammarco, P Chiusolo, G Leone, S Sica
Journal: Leukemia (2007)