tbuckley/cabot-search huggingface dataset:
Chromosomal translocations activating myc sequences and transduction of v-abl are critical events in the rapid induction of plasmacytomas by pristane and abelson virus.
Authors: S Ohno, S Migita, F Wiener, M Babonits, G Klein, J F Mushinski, M Potter
Journal: The Journal of Experimental Medicine (1984)

Plasmacytomas with short latent periods can be induced in BALB/c mice by a single intraperitoneal (i.p.) injection of 0.5 ml pristane followed 20-40 d later by an injection of Abelson virus. The karyotypes of 18 such tumors were determined; 10 of these had rcpt 12;15, 5 had rcpt 6;15 and 3 had no translocations, but two of these have been shown to have interstitial deletions of chromosome 15. The specific breakpoints were the same as described in pristane-induced plasmacytomas, i.e., at 15D2 /3, 6C2 , and 12F2 . Near diploid karyotypes and trisomy of chromosome 11 were frequently seen. All of the Abelson-plus-pristane-induced plasmacytomas (ABPC) were studied as transplanted tumors, contained integrated v- abl sequences, and actively transcribed v- abl mRNA. All but one of these tumors contained abundant myc RNA transcripts. The shortness of the latent periods of the ABPC suggests that the rcpt 12;15 and rcpt 6;15 occur soon after pristane administration and are present at the time Abelson virus is introduced. In this form of plasmacytomagenesis , activated v- abl genes appear to bypass other genetic changes that require a much longer period of time in pristane plasmacytomagenesis . Nonetheless, the consistent finding of chromosome-15 alterations and abundant myc expression in these plasmacytomas emphasize the apparent need for multiple events even in the genesis of some tumors induced by rapid transforming viruses.
Gram Staining of Pneumocystis Sporozoites
Authors: JOHN A. RANKIN
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 June 1984Gram Staining of Pneumocystis SporozoitesJOHN A. RANKIN, M.D., K. RANDALL YOUNG JR., M.D.JOHN A. RANKIN, M.D.Search for more papers by this author, K. RANDALL YOUNG JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-6-919_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Recently, Macher and coworkers (1) have described the usefulness of gram-staining touch preparations of lung biopsy material for the diagnosis ofPneumocystis cariniipneumonia in patients with the acquired immunodeficiency syndrome. This method is more rapid than the conventional staining techniques used to reveal the cystic form of this organism, and the sporozoites are easily visible within "coagula" seen in the touch preparations. Their report prompted us to use the Gram stain on freshly obtained (< 1 hour old) cellular phase material obtained by bronchoalveolar lavage from three patients with suspectedP. cariniipneumonia (subsequently confirmed by...Reference1. MACHERSHELHAMERMACLOWRYPARKERMASUR AJJMH. Pneumocystis carinii identified by Gram stain of lung imprints. Ann Intern Med. 1983;99:484-5. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Yale University School of Medicine New Haven, CT 06510 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAcquired Immune Deficiency Syndrome and the LungDiagnosis ofPneumocystis carinii pneumonia by cytologic evaluation of papanicolaou-stained bronchial specimensCorrection: Letter on Pneumocystis Sporozoites 1 June 1984Volume 100, Issue 6Page: 919-919KeywordsBiopsyBronchoalveolar lavageGram stainingLungsPneumocystisPneumocystis carinii pneumoniaPneumoniaSporozoitesStainingTouch Issue Published: 1 June 1984 PDF DownloadLoading ...
SEVERE DERMATITIS FOLLOWING ULTRA-VIOLET LIGHT
Authors: H. MacCormac, H. M. McCrea
Journal: BMJ (1925)

the nervous mechanism of the arterial wall, and the blood composition or blood content acting directly on the vessel wall.In the earliest stage of toxaemia the arterial system partakes of the general atony, and there is hypomyotonia; but as the blood impurity, being absorbed from the alimen- itary tract, continues to circulate, it acts as an irritant or stimulant to the arterial wall, causing hypermyotonia.It is to be noted, however, that apparently considerable time elapses before permanent hypermyotonia, with changes in the muscular coat, appears, for on taking the blood pressure in these cases it is found to be subnormal, though the artery is hypertonic to the touch.On palpating the brachial artery definite local thickenings are felt in the arterial wall, small portions being affected.This occurred in 20 per cent. of cases examined.
MicroRNA theragnostics for the clinical management of multiple myeloma
Authors: N Ahmad, S Haider, S Jagannathan, E Anaissie, J J Driscoll
Journal: Leukemia (2013)

Theragnostics represent cutting-edge, multi-disciplinary strategies that combine diagnostics with therapeutics in order to generate personalized therapies that improve patient outcome. In oncology, the approach is aimed at more accurate diagnosis of cancer, optimization of patient selection to identify those most likely to benefit from a specific therapy and to generate effective therapeutics that enhance patient survival. MicroRNAs (miRNAs) are master regulators of the human genome that orchestrate myriad cellular pathways to control growth during physiologic and pathologic conditions. Compelling evidence shows that miRNA deregulation promotes events linked to tumor initiation, metastasis and drug resistance as seen in multiple myeloma (MM), an invariably fatal hematologic malignancy. miRNAs are readily detected in body fluids, for example, serum, plasma, urine, as well as circulating tumor cells to demonstrate their potential as readily accessible, non-invasive diagnostic and prognostic biomarkers and potential therapeutics. Specific miRNAs are aberrantly expressed early in myelomagenesis and may more readily detect high-risk disease than current methods. Although only recently discovered miRNAs have rapidly advanced from preclinical studies to evaluation in human clinical trials. The development of miRNA theragnostics should provide widely applicable tools for the targeted delivery of personalized medicines to improve the outcome of patients with MM.
1084. Converting Non-Infectious Virus-Like Particles into Hybrid Gene Therapy Vectors Using Polyethylenimine
Authors: Josh D. Ramsey, Daniel W. Pack
Journal: Molecular Therapy (2006)

Current approaches for delivering genetic material to a target tissue predominately rely on viral or non-viral vectors. Each vector possesses a unique set of advantages and disadvantages. Viral vectors are highly efficient and offer the potential for stable gene expression while nonviral vectors are generally more robust, provide for the possibility of tailored cell targeting, and are less pathogenic and immunogenic. We have explored combining advantages traditionally associated with these two vector types, and possibly reducing disadvantages, through the development of a hybrid viral/nonviral vector based on murine leukemia virus (MLV) virus-like particles (VLP) and high molecular weight branched polyethylenimine (PEI). Non-infectious VLP are produced from cells expressing the MLV gag-pol genes. VLP lack virus envelope protein and thus any means of traversing the cell lipid bilayer. The chimeric hybrid vector that has been developed is an electrostatic complex formed between cationic PEI and negatively charged VLP. PEI functions in place of the virus envelope protein to aid in the endocytic uptake of the complexes and escape from the endolysosomal network. Once in the cell cytoplasm the virus directs intracellular transport to the cell nucleus and integration into the cell genome. Our results show gene expression levels using the hybrid vector range from 20% to 40% those observed using DNA/PEI. The effective diameter of hybrid vector complexes is slightly larger than DNA/PEI complexes (917 nm versus 786 nm), and like DNA/PEI complexes hybrid vector complexes have positive zeta-potentials. Although the transfection efficiency of the hybrid vector is currently less than DNA/PEI, we believe the potential advantages such as tailored cell targeting and stable gene expression warrant the continued study of such hybrid vectors. We will be reporting transfection results for PEI/VLP complexes and characterization of the vector including sizing using dynamic light scattering, surface charge characteristics based zeta- potential measurements, and vector morphology observed in TEM micrographs.
Organellar clusters formed by mitochondrial-rough endoplasmic reticulum associations: An ordered arrangement of mitochondria in hepatocytes
Authors: Joseph Cascarano, Patricia A. Chambers, Eileen Schwartz, Parvoneh Poorkaj, Roy E. Gondo
Journal: Hepatology (1995)

Our objective was to determine if mitochondrial-rough endoplasmic reticulum (mt-RER) associations provide for an ordered arrangement of mitochondria in the cell. If such an ordered arrangement exists, it might be manifested by grouping of mitochondria according to size and biochemical properties. Liver homogenate was subjected to rate zonal centrifugation for fractionating mitochondrial clusters. These clusters were then examined for morphological and biochemical characteristics. Scanning electron microscopy (SEM) showed that (1) mitochondria were held together in clusters by rough endoplasmic reticulum, (2) clusters consisted of mitochondria of comparable size, and (3) a 45-fold difference in average mitochondrial volume existed between the organelles of the fastest and slowest sedimenting clusters. Transmission electron microscopy (TEM) affirmed that all of the organellar clusters examined were mitochondria associated with rough endoplasmic reticulum. Cytochrome oxidase and mitochondrial DNA were found to be proportional to mitochondrial volume, indicating that these components were synthesized in proportion to increases in volume. Conversely, succinic dehydrogenase and ornithine carbamoyl transferase were increased disproportionately (2.9-fold and six-fold, respectively) with increase in mitochondrial volume. It is evident from this biochemical heterogeneity that clusters composed of larger mitochondria differ functionally from clusters of smaller mitochondria. The size-ordered arrangement suggests that this organization is in some way related to the biogenesis of hepatocyte mitochondria. It is also conjectured that the biochemical heterogeneity is a consequence of addition of selected proteins (e.g., succinic dehydrogenase and carbamoyl transferase) to mitochondria in a developmental process as they mature into larger organelles.
Atherosclerosis: A Comparative Study
Authors: R. Finlayson, C. Symons, R. N. T-W-Fiennes
Journal: BMJ (1962)

The diversity of opinion currently held concerning the pathogenesis of atherosclerosis suggested that a com- parative study of spontaneous arterial disease would prove of value in emphasizing any factor common to this condition in animals and man, particularly as experimental methods have failed to reproduce the exact picture of human atheroma.Florey (1960) has discussed the importance of such a study.but apart from Fox (1923, 1933, 1939) and Ratcliffe and Cronin (1958) there have been few reports of the frequency of occurrence and the comparative pathology of athero- sclerosis in any large mixed group of animals.This paper describes our findings from a fairly wide selection of material obtained from the London Zoological Gardens.We have attempted to correlate post-mortem findings with some aspects of dietetic and clinical history and the serum cholesterol obtained after death.
CELLS INVOLVED IN THE IMMUNE RESPONSE
Authors: Nabih I. Abdou, Bram Rose, Maxwell Richter
Journal: The Journal of Experimental Medicine (1969)

By appropriate irradiation and cell transfer experiments, a direct correlation was observed between the presence of viable and immunologically active antigen-reactive cells and the capacity of the rabbits to respond following immunization. Rabbits given 800 R total body irradiation were unable to elicit a humoral immune response nor did they possess significant numbers of antigen-reactive cells. The ability to respond with humoral antibody formation did not reappear until antigen-reactive cells could be detected. These results strongly indicate that the presence of competent antigen-reactive cells are necessary for the successful induction of the humoral immune response in the rabbit.
Assessment of Clofazimine Activity in a Second-Line Regimen for Tuberculosis in Mice
Authors: Jacques H. Grosset, Sandeep Tyagi, Deepak V. Almeida, Paul J. Converse, Si-Yang Li, Nicole C. Ammerman, William R. Bishai, Donald Enarson, Arnaud Trébucq
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Although observational studies suggest that clofazimine-containing regimens are highly active against drug-resistant tuberculosis, the contribution of clofazimine for the treatment of this disease has never been systematically evaluated.Objectives: Our goal was to directly compare the activity of a standard second-line drug regimen with or without the addition of clofazimine in a mouse model of multidrug-resistant tuberculosis. Our comparative outcomes included time to culture conversion in the mouse lungs and the percentage of relapses after treatment cessation.Methods: Mice were aerosol-infected with an isoniazid-resistant (as a surrogate of multidrug-resistant) strain of Mycobacterium tuberculosis. Treatment, which was administered for 5 to 9 months, was initiated 2 weeks after infection and comprised the following second-line regimen: daily (5 d/wk) moxifloxacin, ethambutol, and pyrazinamide, supplemented with amikacin during the first 2 months. One-half of the mice also received daily clofazimine. The decline in lung bacterial load was assessed monthly using charcoal-containing agar to reduce clofazimine carryover. Relapse was assessed 6 months after treatment cessation.Measurements and Main Results: After 2 months, the bacillary load in lungs was reduced from 9.74 log10 at baseline to 3.61 and 4.68 in mice treated with or without clofazimine, respectively (P < 0.001). Mice treated with clofazimine were culture-negative after 5 months, whereas all mice treated without clofazimine remained heavily culture-positive for the entire 9 months of the study. The relapse rate was 7% among mice treated with clofazimine for 8 to 9 months.Conclusions: The clofazimine contribution was substantial in these experimental conditions.
The Care of HIV-Infected Adults in the United States
Authors: Samuel A. Bozzette, Sandra H. Berry, Naihua Duan, Martin R. Frankel, Arleen A. Leibowitz, Doris Lefkowitz, Carol-Ann Emmons, J. Walton Senterfitt, Marc L. Berk, Sally C. Morton, Martin F. Shapiro, Ronald M. Andersen, William E. Cunningham, Marvin Marcus, Neil S. Wenger, Leslie A. Athey, Stephen M. Smith, Eric G. Bing, Julie A. Brown, M. Audrey Burnham, Dana P. Goldman, David E. Kanouse, Joan W. Keesey, Daniel F. McCaffrey, Judith F. Perlman, Mark A. Schuster, Paul D. Cleary, John A. Fleishman, Ron D. Hays, J. Allan McCutchan, Douglas Richman
Journal: New England Journal of Medicine (1998)

In order to elucidate the medical care of patients with human immunodeficiency virus (HIV) infection in the United States, we randomly sampled HIV-infected adults receiving medical care in the contiguous United States at a facility other than a military, prison, or emergency department facility during the first two months of 1996. We interviewed 76 percent of 4042 patients selected from among the patients receiving care from 145 providers in 28 metropolitan areas and 51 providers in 25 rural areas.
Serum albumin concentration, arm circumference, and oedema and subsequent risk of dying in children in central Africa.
Authors: M Dramaix, P Hennart, D Brasseur, P Bahwere, O Mudjene, R Tonglet, P Donnen, R Smets
Journal: BMJ (1993)

OBJECTIVE--To measure the prognostic value of clinical, anthropometric, and biological indicators of protein energy malnutrition in hospitalised children. DESIGN--Hospital based follow up study from admission to discharge or death of a cohort of children. SETTING-Paediatric hospital in Zaire. SUBJECTS--1129 children consecutively admitted between August 1986 and October 1988. MAIN OUTCOME MEASURES--Height, weight, arm circumference, skinfold thicknesses, serum albumin concentration, and mortality. RESULTS--Mortality was higher in wasted children and in those with a mid-upper arm circumference &lt; 125 mm, a serum albumin concentration &lt; 16 g/l, and oedema. After multivariate analysis, serum albumin concentration was the best predictor of subsequent risk of dying. Mid-upper arm circumference and oedema, however, still contributed considerably to evaluation of mortality. CONCLUSIONS--In this specific environment of central Africa an isolated clinical sign such as oedema is not enough to detect children with a high risk of dying among those admitted to paediatric wards with severe protein energy malnutrition. Measurement of additional indicators such as arm circumference and serum albumin concentration seems to be of crucial importance.
Antiretroviral Therapy for Previously Treated Patients
Authors: Julio S.G. Montaner, John W. Mellors
Journal: New England Journal of Medicine (2001)

Combination therapy with three antiretroviral drugs improves the outcome of patients infected with human immunodeficiency virus type 1 (HIV-1) and has led to sustained decreases in AIDS-related morbidity and mortality in North America and Europe.13 Long-overdue attention has recently focused on providing this lifesaving therapy to persons with HIV-1 infection in developing countries.4 But even under ideal circumstances, current antiretroviral therapy has substantial limitations. Foremost among them are side effects of the medications and incomplete suppression of HIV-1 replication, which allows the emergence of drug-resistant variants of HIV-1.Antiretroviral therapy is most effective the first time it is prescribed. . . .
Role of drugs in fractures of the femoral neck.
Authors: S Rashiq, R F Logan
Journal: BMJ (1986)

To investigate the role of drugs in the rising incidence of fractures of the femoral neck in the elderly a case-control study inquiring about the use of prescribed drugs was carried out. The drug histories of 102 patients with femoral neck fractures were obtained from general practice records and compared with those of 204 controls matched for age and sex from the same practices. At the time of fracture 41 patients with fractures and 126 controls were receiving at least one prescription (relative risk of fracture of the femoral neck in patients taking drugs = 0.42, p = 0.0006). For all types of prescribed drugs except antibiotics the risk of fracture of the femoral neck was less in patients taking drugs than in those not doing so, and this was true at all times in the year before fracture. Six patients with fractures were receiving thiazide diuretics compared with 37 controls (relative risk 0.28, p = 0.004). These results indicate that, contrary to popular belief, drugs that sedate or that impair postural control are not important factors in fractures of the femoral neck. The results are consistent with the hypothesis that the hypocalciuria induced by thiazides protects against fracture, but the degree of protection is not significantly greater than that associated with other drugs.
EFFECT OF RENAL IMPAIRMENT IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION WITH SIROLIMUS-ELUTING STENTS VERSUS PACLITAXEL-ELUTING STENTS.
Authors: KENNOSUKE YAMASHITA, Masahiko Ochiai, Kazuhiro Ashida, Tadayuki Yakushiji, Myong Hwa Yamamoto, Shigeo Saito, Koichi Hoshimoto, Yuki Mikoshiba, Naoei Isomura, Hiroshi Araki, Chiaki Obara
Journal: Journal of the American College of Cardiology (2010)
Serotonin Receptors and Headache
Authors: Neil H. Raskin
Journal: New England Journal of Medicine (1991)

About 30 years ago, the hypothesis that serotonin (5-hydroxytryptamine) was important to the pathogenesis of migraine caused great excitement. Methysergide had been found to antagonize certain peripheral actions of 5-hydroxytryptamine and had been introduced as the first drug capable of preventing or reducing the intensity and frequency of migraine attacks.1 Subsequent studies revealed that platelet levels of 5-hydroxytryptamine fall consistently at the onset of headache and that migrainous episodes may be triggered by drugs releasing 5-hydroxytryptamine.2 Such changes in circulating levels proved to be pharmacologically trivial, however, and interest in the humoral role of 5-hydroxytryptamine in migraine declin d. Today, . . .
Dr A will see you now
Authors: Colin Douglas
Journal: BMJ (2005)

He will see you now. He may not see what you really want him to see, or even what you think he ought to see for himself, but he will see you, and he will almost certainly do his best.

But Dr A will see you through a glass darkly; and just how darkly will depend on the degree of his impairment, which may be anything from a minor blunting of empathy to total emotional colour blindness. …
The Search for the Ultimate Cause of Maleness
Authors: Kenneth K. Kidd
Journal: New England Journal of Medicine (1985)

From the time of the first studies of human sex-chromosome anomalies it has been clear that sex determination in human beings is largely a function of the presence or absence of a Y chromosome; the Y chromosome is both necessary and sufficient for male development. Exceptions to that rule have been the primary resource for learning what specific genetic information on the Y chromosome is responsible for maleness and how that information diverts the developmental cascade. These questions have been the foci of numerous scientific studies in the past few decades. The paper by Kiel-Metzger et al.1 in the current . . .
Effect of ischemia–reperfusion on heart mitochondria from hyperthyroid rats
Authors: P Venditti
Journal: Cardiovascular Research (2002)

We investigated the effect of hyperthyroidism on the functional response of mitochondria to ischemia-reperfusion and its relationship with changes in mitochondrial susceptibility to stress conditions.Hyperthyroidism was elicited by ten daily intraperitoneal injections of T3 (10 microg/100 g body weight). Mitochondria were isolated at 3000xg (M3) from homogenates of hearts perfused by the Langendorff technique after either 25 min reperfusion following 20 min ischemia or 45 min perfusion (controls). Rates of O2 consumption and H2O2 release with complex II-linked substrate, capacity to remove H2O2, extent of oxidative damage, levels of liposoluble antioxidants, such as ubiquinols and vitamin E, and susceptibility to Ca2+ -induced swelling were determined.During reperfusion, hyperthyroid hearts displayed a significant tachycardia together with a low functional recovery. In comparison to the respective controls, mitochondria from both euthyroid and hyperthyroid hearts subjected to ischemia-reperfusion protocol exhibited decreases in the rate of O2 consumption, capacity to remove H2O2, and concentration of antioxidants, and increases in the rate of H2O2 release, concentration of hydroperoxides and protein-bound carbonyls, and susceptibility to Ca2+ -induced swelling. Such changes were higher in mitochondria from hyperthyroid hearts. The increase in the protein percent content and cytochrome oxidase activity of a mitochondrial fraction isolated at 8000xg (M8) from hyperthyroid hearts after reperfusion, suggests that the decline of mitochondrial respiration of M3 fraction could be due to the degradation of the oldest, mature mitochondria endowed of high oxidative capacity, but low antioxidant capacity, which would be lost by heavy mitochondrial fraction and recovered in the light fraction.The higher susceptibility to ischemia-reperfusion of the heart from hyperthyroid animals is associated with a significant increase in mitochondrial dysfunction.