tbuckley/cabot-search huggingface dataset:
Soluble tumor necrosis factor receptor inhibits interleukin 12 production by stimulated human adult microglial cells in vitro.
Authors: B Becher, V Dodelet, V Fedorowicz, J P Antel
Journal: Journal of Clinical Investigation (1996)

IL-12 is a cytokine detected in active lesions in multiple sclerosis (MS) and promotes the acquisition of a Th1 cytokine profile by CD4+ T cells. Autoreactive T cells recovered from the central nervous system of animals with experimental autoimmune encephalomyelitis (EAE), a disease model for MS, display this phenotype. We demonstrate that human central nervous system-derived microglia, but not astroglia, can produce IL-12 in vitro. Under basal culture conditions, human adult microglia do not express detectable levels of IL-12, although these cells show some degree of activation as assessed by expression of the immunoregulatory surface molecules HLA-DR and B7 as well as low levels of TNF-alpha mRNA. Following activation with LPS, IL-12 p40 mRNA and p70 protein can be readily detected. IL-12 production is preceded by TNF-alpha production and is inhibited by recombinant soluble human TNF receptor (II)-IgG1 fusion protein (shu-TNF-R). These data indicate regulation of IL-12 by an autocrine-dependent feedback loop, providing an additional mechanism whereby shu-TNF-R, now used in clinical trials in MS, may be exerting its effect.
517. Lipopolythioureas: Non Cationic System for Gene Delivery
Authors: Jeanne Leblond, Nathalie Mignet, Maria-Vittoria Spanedda, Daniel Scherman, Jean Herscovici
Journal: Molecular Therapy (2006)

The positive charge of cationic-lipid/DNA cationic polymer/DNA complexes renders them highly susceptible to interactions with the biological milieu, leading to aggregation and destabilization, and rapid clearance from the blood circulation. To overcome such drawback we have investigated the possibility to deliver DNA using non- cationic synthetic vectors. We have previously demonstrated that neutral lipopolythioureas DT3TU bind to DNA leading to small particles. These new DNA binding agents lack non-specific accumulation in the lung and increasing circulation time in the bloodstream compared to cationic liposomes. However DT3TU is highly hydrophobic and are inefficient for gene delivery. To improve lipopolythiourea efficiency we have synthesized a series of new lipopolythioureas (LPT) build around two di-thiourea scaffolds derived from (2-amino-3-thiocarbamoylamino- propyl)thiourea or from 2,6-bis(thiocarbamoylamino)hexanoic acid. Variation of hydrophobic anchor size and linker has also been investigated. We have found that derivative ended with an N-diol could be formulated without helper lipid. On the other hand LPT with methyl terminus yielded also small particles when formulated with DPPC. Ten compounds were evaluated for their transfection efficiency against B16 or Eahycell line in the presence of serum. The results revealed that (2-amino-3-thiocarbamoylamino-propyl)thioureas, elicited transfection activity with the same level as cationic lipids. Intratumoral injection of thiourea lipoplex was used to evaluate gene expression on 3LL tumor in C57BL\6 mice. The luciferase reporter gene revealed that LPT express the protein with a similar level as cationic lipid. Finally, pharmacokinetics and biodistribution in mice showed that 10 % of the complexes were still circulating after two hours (3% for other cationic lipid vectors). To the best of our knowlege these new LPT are the first examples of non-cationic transfecting lipids.
Man-made Death
Authors: Richard B. Johnson
Journal: JAMA (1989)

To the Editor.—  In enumerating the causes of man-made deaths, Mr Rhodes1omits the second most common cause (after war) of man-made deaths in this century: the incompetent centralized management of the economy. The peacetime mortality caused by the Great Leap Forward in China (20 to 30 million excess deaths) and the collectivization of the Ukraine (8 to 12 million excess deaths) dwarfs the number of man-made deaths due to guerilla conflicts, political repression, torture, and capital punishment.
A Case of Esophageal Obstruction after Ingestion of a Granular Laxative
Authors: B. Vergeau, C. Nizou, J. M. Ciribilli, G. Grandpierre
Journal: Endoscopy (1995)

See also: Endoscopic Diagnosis and Treatment of an Esophageal Bezoar Resulting from Bulk Laxative IngestionEndoscopy 1994; 26(08): 710-710DOI: 10.1055/s-2007-1009074
Functional Significance of Using Tissue Adhesive Substance in Nephron-Sparing Surgery: Assessment by Quantitative SPECT of 99m Tc-Dimercaptosuccinic Acid Scintigraphy
Authors: Guy Hidas, Liad Lupinsky, Alexander Kastin, Boaz Moskovitz, David Groshar, Ofer Nativ
Journal: European Urology (2006)
The Fear of Looking: Or Scopophilic-Exhibitionistic Conflicts
Authors: ILZA VEITH
Journal: JAMA (1975)

It seems surprising that a book of hardly 140 pages should be subdivided into six sections and still adequately and satisfactorily deal with the normal and abnormal famifications of active and passive voyeurism. The definition of scopophilia and the description of the neurotic consequences of the scopophilic-exhibitionistic transgressions originate in the workings of Freud and it was for this reason that Dr. Allen, a psychoanalyst, discerned many such neuroses in his patients and was able to illustrate his monograph with a dozen highly pertinent case histories. Freud's authorship in this subject matter places a limit on the depth of Dr. Allen's exploration of the historical background of the symptom complex of scopophilia-exhibitionism; nevertheless, the historical survey is entirely acceptable from the psychoanalytical point of view. Altogether, this is a well written and highly entertaining book of great interest to the psychiatrist, the social historian, the historian of art, and the
Small bowel resistances and the gastroduodenal brake.
Authors: N J Parr, J S Grime, J N Baxter, M Critchley, C R Mackie
Journal: Gut (1987)

Osmoreceptors in the upper small bowel may delay gastric emptying by inhibiting fundal tone and/or by increasing outflow resistances. In this study we examined the contribution of postpyloric resistances to this braking system. Seven dogs had gastric emptying of 250 ml 15% dextrose, labelled with 99mTc-DTPA, measured by gamma camera imaging (preoperative studies: n = 21). A proximal duodenal cannula was inserted and studies repeated in four modes: with the cannula closed (n = 14); with total diversion of gastric effluent through the cannula (n = 7); with diversion and downstream reinstillation of effluent at a constant rate (n = 14) equivalent to emptying calculated from studies without diversion; and with diversion and total reinstillation of effluent (n = 14). Gastric emptying at 90 minutes was similar in preoperative studies (48 +/- 5% - mean +/- SEM) and in those with the cannula closed (50 +/- 3%). By comparison 9total diversion9 produced rapid emptying over 90 minutes (97 +/- 1%; p less than 0.001). Reinstillation of effluent at a constant rate reduced the 90 minute emptying to 59 +/- 6%, and total reinstillation slowed emptying further to 37 +/- 4% (p less than 0.05). Neither reinstillation protocol yielded gastric emptying rates that were significantly different from those in studies without diversion. With total reinstillation, emptying and hence reinstillation rates were more variable, proceeding in a step and plateau fashion. We conclude that canine jejunal osmoreceptor activity is mediated through the stomach, with postpyloric resistances playing little or no role. Gastric emptying curve analysis suggested that increments of rapid small bowel filling provoke exaggerated braking responses.
Research Funding, Myocardial Infarction Triggers Among Areas of Concern Addressed at AHA Forum
Authors: Phil Gunby
Journal: JAMA (1996)

CARDIOVASCULAR disease research, says the president of the American Heart Association (AHA), poses a paradox. Heart-related disease, says AHA President Jan L. Breslow, MD, seems to be slipping from the attention of the American public. Or, if Americans do pause to ponder cardiovascular disease, many are coming to regard it as an elderly person's malady and perhaps even a good way to die. What's more, politicians and some scientists in policymaking positions now are underfunding cardiovascular research, Breslow contends. He says this may be because—in seeking support— scientists have oversold the success of surgery, drugs, and increased knowledge of cardiovascular disease processes that have improved patient care and outcomes. Now, says Breslow, who is Leonhardt Professor, Rockefeller University, New York, NY, it's time to stop broadcasting those successes and emphasize that heart disease still is the No. 1 killer of people in this country and stroke is No. 3. Also
Abnormal expression of PDC-E2 on the apical surface of biliary epithelial cells in patients with antimitochondrial antibody-negative primary biliary cirrhosis
Authors: Koichi Tsuneyama, Judy van de Water, David van Thiel, Ross Coppel, Boris Ruebner, Yasuni Nakanuma, Rolland E. Dickson, Eric M. Gershwin
Journal: Hepatology (1995)

The presence of antimitochondrial antibodies (AMA) is a major criterion for the diagnosis of primary biliary cirrhosis (PBC). Although it is not clear that AMA are involved in the pathogenesis of the disease, the study of these autoantibodies has enabled much information to be accumulated about the specificity of this response. The autoantigens have been identified as components of a functionally related enzyme family, the 2-oxo-acid-dehydrogenase complex. Within this complex, pyruvate dehydrogenase E2 subunit (PDC-E2) has been determined to be the immunodominant autoantigen. Using a panel of mouse monoclonal antibodies and human combinatorial autoantibodies, it has been demonstrated that patients with PBC, but not controls, have an abnormal expression of either PDC-E2 or a cross-reacting molecule in the apical region of biliary epithelium. Others have shown a similar reaction using rabbit sera directed to PDC-E2. Our previous studies have concentrated on AMA-positive patients. In this study, the presence of PDC-E2, class II, immunoglobulin (Ig) A, and B7/BB1 in the bile duct epithelial cells of AMA-positive as well as AMA-negative patients is addressed. Most patients with AMA-negative PBC (seven of nine) react in a fashion similar to AMA-positive patients with intense staining of the apical region of the bile duct epithelial cells of "PDC-E2," increased IgA expression, and little major histocompatibility complex (MHC) class II staining in the early-stage patients. Interestingly, the two AMA-negative patients that did not express PDC-E2 on the apical side of their biliary epithelium had anticentromere antibodies and Sjögren's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
The UGDP Study
Authors: W. M. Hubbard
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The lead editorial in the Feb 10 issue ofThe Journal(231:624, 1975) distorted the careful and scholarly Biometric Society Committee report<sup>1</sup>on its statistical analysis of the University Group Diabetics Program (UGDP)<sup>2</sup>data. The author of the editorial declared, "The probability that oral hypoglycemic agents cause premature deaths from cardiovascular disease remains valid." However, the Committee report found: The possibility that deaths may have been allocated to cardiovascular causes preferentially in the groups receiving oral therapy exists and in view of the "nonsignificance" of differences in total mortality, some reservations about the conclusion that oral hyperglycemics [sic] are toxic must remain. Nonetheless, we consider the evidence of harmfulness moderately strong. The author of the editorial also offered an "estimate that 10,000 to 15,000 such unnecessary deaths occur each year in the United States alone" as a result of these drugs. This statement was the
Identification of Human Aldehyde Dehydrogenase 1 Family Member A1 as a Novel CD8+ T-Cell–Defined Tumor Antigen in Squamous Cell Carcinoma of the Head and Neck
Authors: Carmen Visus, Diasuke Ito, Andrew Amoscato, Malgorzata Maciejewska-Franczak, Ahmed Abdelsalem, Rajiv Dhir, Dong M. Shin, Vera S. Donnenberg, Theresa L. Whiteside, Albert B. DeLeo
Journal: Cancer Research (2007)

Abstract Few epitopes are available for vaccination therapy of patients with squamous cell carcinoma of the head and neck (SCCHN). Using a tumor-specific CTL, aldehyde dehydrogenase 1 family member A1 (ALDH1A1) was identified as a novel tumor antigen in SCCHN. Mass spectral analysis of peptides in tumor-derived lysates was used to determine that the CTL line recognized the HLA-A*0201 (HLA-A2) binding ALDH1A188-96 peptide. Expression of ALDH1A1 in established SCCHN cell lines, normal mucosa, and primary keratinocytes was studied by quantitative reverse transcription-PCR and immunostaining. Protein expression was further defined by immunoblot analysis, whereas ALDH1A1 activity was measured using ALDEFLUOR. ALDH1A188-96 peptide was identified as an HLA-A2–restricted, naturally presented, CD8+ T-cell–defined tumor peptide. ALDH1A188-96 peptide-specific CD8+ T cells recognized only HLA-A2+ SCCHN cell lines, which overexpressed ALDH1A1, as well as targets transfected with ALDH1A1 cDNA. Target recognition was blocked by anti-HLA class I and anti-HLA-A2 antibodies. SCCHN cell lines overexpressing ALDH1 had high enzymatic activity. ALDH1A1 protein was expressed in 12 of 17 SCCHN, and 30 of 40 dysplastic mucosa samples, but not in normal mucosa. ALDH1A1 expression levels in target cells correlated with their recognition by ALDH1A188-96 peptide-specific CD8+ T cells. Our findings identify ALDH1A1, a metabolic antigen, as a potential target for vaccination therapy in the cohort of SCCHN subjects with tumors overexpressing this protein. A smaller cohort of subjects with SCCHN, whose tumors express little to no ALDH1A1, and thus are deficient in conversion of retinal to retinoic acid, could benefit from chemoprevention therapy. [Cancer Res 2007;67(21):10538–45]
Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.
Authors: K Aalto-Setälä, C L Bisgaier, A Ho, K A Kieft, M G Traber, H J Kayden, R Ramakrishnan, A Walsh, A D Essenburg, J L Breslow
Journal: Journal of Clinical Investigation (1994)

Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system.
Variables predictive of performance in elite middle-distance runners.
Authors: W L Kenney, J L Hodgson
Journal: British Journal of Sports Medicine (1985)

The purpose of this study was to investigate possible factors which may account for differences in performance times within a closely-matched group (in terms of performance) of elite distance runners. The runners were training for competition in the 1984 Olympic Games in either the 5000 m or the 3000 m steeplechase events. Each runner's best performance time (BPT) was obtained and a stepwise regression analysis was performed with the following independent variables: age, weight, % body fat, VO2 max, aerobic threshold (AerT), and anaerobic threshold (AnT). For the 5000 m-runners, a multiple correlation of age and AnT accounted for 77% of the variance (p less than 0.02); for the 3000 m steeplechase runners, body weight alone and body weight and AnT accounted for 94% (p less than .01) and 98% (p less than .05) of the variance, respectively. The results suggest that, among elite middle-distance runners, these parameters deserve attention as potential predictors of performance.
Probing the Endocytic Pathways of the Filamentous Bacteriophage in Live Cells Using Ratiometric pH Fluorescent Indicator
Authors: Ye Tian, Man Wu, Xiangxiang Liu, Zhi Liu, Quan Zhou, Zhongwei Niu, Yong Huang
Journal: Advanced Healthcare Materials (2014)

Viral nanoparticles have attracted extensive research interests in diverse applications of diagnosis and therapy. In particular, filamentous M13 bacteriophages have shown great potential in biomedical applications. However, its pathways entering into cells still remain unclear, and this greatly hinders its further use as a drug or gene carrier. Here, a ratiometric M13 pH probe is designed by conjugating two fluorescent dyes onto the surface of M13. Since the intensity ratio is not influenced by probe concentration, ion strength, temperature, photobleaching, and optical path length, this ratiometric probe can be used to investigate the intracellular pH map of M13. More importantly, the internalization mechanism of M13 can be elucidated. It is found that this filamentous phage shows great cell‐type dependence in interaction with cells and internalization mechanism. The phage tends to be bounded on the cell membrane of only epithelial cells, not endothelial cells. Furthermore, the M13 phage enters into cells through endocytosis with specific mechanism: clathrin‐mediated endocytosis and macropinocytosis for HeLa; vesicular transport, clathrin‐mediated endocytosis, and macropinocytosis for MCF‐7; caveolae‐mediated endocytosis for human dermal microvascular endothelial cell (HDMEC). This work provides key notes for cancer diagnosis and therapy based on filamentous bacteriophage, especially for design of pH‐sensitive drug delivery systems.
Patient Outcomes Following Tricompartmental Total Knee Replacement
Authors: Christopher M. Callahan, Brenda G. Drake, David A. Heck, Robert S. Dittus
Journal: JAMA (1994)

To provide estimates of patient outcomes following tricompartmental knee replacement and to examine variation in outcomes due to patient and prosthesis characteristics.English-language articles identified through a computerized literature search and bibliography review.Studies were included if they enrolled 10 or more patients at the time of initial knee replacement and measured patient outcomes using a global knee-rating scale.Each study was subjected to a blinded qualitative assessment and unblinded abstraction of patient characteristics, surgical techniques, and outcomes.A total of 130 studies reporting patient outcomes on 154 cohorts satisfied inclusion criteria. The total number of enrolled patients was 9879 with a mean enrollment of 64.1 patients. The mean follow-up was 4.1 years. The mean patient age was 65.0 years, 71.7% of patients were women, 62.6% had osteoarthritis, and 26.6% underwent bilateral knee replacement. Global rating scale scores improved by 100% for the typical enrolled patient, and 89.3% of patients reported good or excellent outcomes. Anatomic classification of the prosthesis, percentage of enrolled patients with osteoarthritis, publication year, and number of enrolled patients explained 27% of the variation in reported mean postoperative global rating scale scores. The weighted mean complication rate was 18.1%, and the mean mortality rate per year of follow-up was 1.5%. The overall rate of revision during 4.1 years was 3.8%.Tricompartmental knee replacement was a safe and effective procedure for the patients reported in these studies. The knee pathology and the type of prosthesis were significant predictors of outcomes. Limitations in the reporting style of these articles severely constrain the ability to explore variation in outcomes due to study, patient, or prosthesis characteristics and restrict their generalizability.
On the Medical Services of the Navy and Army from the Accession of Henry VIII to the Restoration
Authors: W. R. E. Smart
Journal: BMJ (1874)

In some (diseases the couirse of the temperature may be said to be typical, in others less typical, and in some there may be an absenice of anly typical character.Even in this last case, however, the very absence of certain points may assist the diagnosis.Departur-es from the typical course in a disease ou-lht, here as elsewhere, to excite suspicionl, and the thermometer may inidicate a coming danger before any mischief or com- plication can be (letected as the explanation of the disturbance-Some- timiies, no doubt, the alarm may seem to have beena false one, for no obvious complication may appear to justify the warning ; but this, no doubt, arises from the imperfection of our methods of research, and even inl stlch a case the exacerbation has a meaning which should not be despise(l.Alonig w-ith the pulse, the temperature will be found a most valuable gulide in all acute diseases.As a rule, the two wvill be foutd to go up anld down together ; butt sometimes a rise or fall in the one will have its significance muclh affected by a due consideration of the behaviour of the other ; they both stanid closely related to the most important operations going on in the hulmiani body wvhether in health or disease.By the bril- liant achievemiients of physical diagnosis, we often obtain the evidence of mischief done andI of organs changed * but by means of the temperature, when wisely used anid coinsideredl in its relationship with all the circum- stanices andI conditions of the patienlt, we frequently get a revelation of the state of tuirmoil which may result in these physical changes, and so wAe may sometimiies be enabled to foresee the dangers, ancd perhaps to apply the remedy in time.
THE IMMUNOLOGICAL DEVELOPMENT OF THE HUMAN FETUS
Authors: R. van Furth, Henrica R. E. Schuit, W. Hijmans
Journal: The Journal of Experimental Medicine (1965)

The immunogenesis of the human fetus has been investigated by means of the formation of immunoglobulins in vitro, immunofluorescence, morphological studies, and analysis of the immunoglobulins in the serum. Twenty fetuses which were born alive but died soon after delivery, were studied; their ages ranged from 13 to 31 weeks. The results of the spleen cultures demonstrated the synthesis of IgG and IgM, which starts at about the twentieth week of gestation. In the serum, IgM could be detected at about the same period. The immunofluorescent staining of the spleen tissue showed that medium sized and large lymphoid cells as well as plasma cells, even with Russell bodies, were positive for either IgG or IgM. The peripheral blood was also found to contain a small number of medium sized IgG and IgM-positive cells. Both the spleen and the peripheral blood showed a considerable number of fluorescent small lymphocytes which exclusively contained IgM. The relatively high ratio of IgM to IgG production prenatally as compared to the postnatal situation, agrees with a predominantly primary antibody response in fetal life. In general, the fetal thymus did not synthesize immunoglobulins. No indications for the synthesis of IgA and IgD during fetal life were found.