tbuckley/cabot-search huggingface dataset:
Even 'in perspective,' HIV specter haunts health care workers most
Authors: M. F. Goldsmith
Journal: JAMA (1990)

WORK HARDER at preventing a blood-borne disease for which potential protection is being largely ignored, worry less about getting one that is proving to be transmitted relatively seldom in hospitals—but don't let down your guard for a minute. This is the burden of advice from physicians on the front line against the acquired immunodeficiency syndrome, presented at the first Hopkins Conference on AIDS, put on last month in Baltimore, Md, by The Johns Hopkins Medical Institutions. During a discussion of relative risk for human immunodeficiency virus (HIV) infection in health care workers, David Henderson, MD, associate director of the Warren G. Magnuson Clinical Center at the National Institutes of Health, drew a comparison between hepatitis B and HIV infection. He said, "If you have 1000 exposures to somebody who is antigen-positive for hepatitis B, you will have 270 to 430 infections and certainly 3 to 5 of those individuals will
RED CELL STROMA IN DOGS
Authors: F. S. Robscheit-Robbins, G. H. Whipple
Journal: The Journal of Experimental Medicine (1955)

Normal red blood cells in dogs contain stroma in fairly uniform amounts. This red cell stroma is rich in proteins and lipides. Anemia due to blood loss causes an increase in stroma protein. The highest levels of stroma protein are found in the severe anemias. As the anemia is corrected by red cell regeneration, the stroma protein level falls to normal. Anemia due to blood destruction (phenylhydrazine) presents very high levels of stroma protein-almost double the increase noted in anemia due to blood loss. Hypoproteinemia added to anemia due to blood loss causes no significant change on the stroma protein level. Abscesses due to the subcutaneous injection of turpentine during the anemia cause slight decreases in the stroma protein levels. Chloroform poisoning has no effect on the stroma protein levels. The total lipides of the stroma are rather stable and are little influenced by anemia. In certain experiments with hemolytic anemia and with hypoproteinemia, there is a significant rise in total lipide figures.
USPIO-labeled textile materials for non-invasive MR imaging of tissue-engineered vascular grafts
Authors: Marianne E. Mertens, Sabine Koch, Philipp Schuster, Jakob Wehner, Zhuojun Wu, Felix Gremse, Volkmar Schulz, Lisanne Rongen, Frederic Wolf, Julia Frese, Valentine N. Gesché, Marc van Zandvoort, Petra Mela, Stefan Jockenhoevel, Fabian Kiessling, Twan Lammers
Journal: Biomaterials (2014)
Abstract 2040: Indication switching of the FDA-approved anticancer tyrosine kinase inhibitors to treat metabolic diseases.
Authors: Jiazhi Sun, Lun Yang, Minghua Li, Zhixin Wang, Amy Haynes, Qian Wang, Isaac Raplee, Jean Melchisedek, Anand Prasad, Kevin B. Sneed, Lin He, Shufeng Zhou
Journal: Cancer Research (2013)

Abstract Drug switching is a unique way to identify and extend new indications for approved drugs in drug discovery &amp; development. Tyrosine kinase inhibitors (TKIs) are used in biologically targeted cancer therapy and so far 12 TKIs have been approved by FDA. We hypothesize that these TKIs act on other molecular targets in addition to tyrosine kinases and may manage metabolic diseases given that there is a complex network of kinases that work together to regulate a number of important cellular processes. Employing a comprehensive docking method with our established chemical-protein interactome (CPI) and 11 FDA-approved TKIs, we have discovered301 PDB-deposited proteins corresponding to 353 ligand binding pockets among a total of 1,780 PDB-deposited human protein entries. Notably, sorafenib, dasatinib and crizotinib had a CPI binding score (ZZ_score) of -1.2903, -1.0278 and -1.5384 against histone deacetylase 7A, respectively. In addition, those TKIs achieved high ZZ scores against B-Raf, PPAR and VDR, suggesting a high binding affinity of sorafenib, dasatinib and crizotinib with these proteins. Our preliminary studies have showed that the acetylated-lysine in α-tublin and oncogenic Akt and Raf-signaling was inhibited significantly in human multiple melanoma cells by these TKIs. Interestingly, dasatinib increased VDRE and HDLR luciferase reporter activity in the human lung adenocarcinoma A-549 cells, and dasatinib and crizotinib induced autophage by activated LC3 in vitro. Furthermore, the erlotinib and sorafenib decreased glucose levels in Wistar STZ-D rats. These TKIs are predicted to act on a series of therapeutics targets associated with metabolic diseases (such as PPAR and Sirt1). Collectively, FDA-approved TKIs may be switched to become a “magic bullet” concurrently targeting tyrosine kinase, HDAC, PPAR, VDR and B-Raf, shedding a light for future anti-metabolic disorder and anticancer drug discovery &amp; development. Further validation of additional “hot targets” besides tyrosine kinase such as HDAC, B-Raf, PPAR, Sirt1, Akt and VDR, and in vivo evaluation of anti-metabolic disorder by TKIs are undergoing at our laboratory. These findings suggest that drug switching may represent a new and effective approach to expanding the application of existing drugs. Citation Format: Jiazhi Sun, Lun Yang, Minghua Li, Zhixin Wang, Amy Haynes, Qian Wang, Isaac Raplee, Jean Melchisedek, Anand Prasad, Kevin B. Sneed, Lin He, Shufeng Zhou. Indication switching of the FDA-approved anticancer tyrosine kinase inhibitors to treat metabolic diseases. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2040. doi:10.1158/1538-7445.AM2013-2040
Effect of alanine on ?-galactosamine-induced acute liver failure in rats
Authors: K Maezono
Journal: Hepatology (1996)

The effect of high-dose alanine on survival and liver function in rats with acute liver failure caused by a lethal dose of D-galactosamine (D-gal) was studied. Greater than 90% of control animals died within 5 days after D-gal injection, but alanine significantly decreased mortality, even when treatment was started at 12 hours after D-gal injection. Alanyl-glutamine had a slight effect, but glucose produced no improvement. There was marked elevation of the plasma aspartate transaminase (AST) level, prolongation of the prothrombin time, and a decrease of the arterial ketone body ratio (AKBR) and hepatic adenosine triphosphate (ATP) content within 12 hours after D-gal injection. The AKBR decreased in parallel with the decrease of the hepatic ATP content. These parameters were significantly improved in alanine-treated rats at 48 hours after the induction of liver damage, which was just before control rats began to die. The hepatic ATP content was significantly greater in alanine-treated rats than in the other rats (including normal controls), but glucose pretreatment had no effect. It was also found that the liver labeling index of partially hepatectomized rats was significantly elevated by alanine administration at 3 hours before measurement. In conclusion, alanine is effective for the treatment of experimental acute liver failure, probably caused by promotion of ATP synthesis. Ala may be a good candidate for clinical application because of its preventive effect on hepatocyte necrosis and its promotive effect on liver regeneration.
Detection of Renovascular Hypertension with Angiotensin II Blockade
Authors: LESLIE BAER
Journal: Annals of Internal Medicine (1977)

Angiotensin II blockade with sarcosine1-alanine8-angiotensin II (saralasin, P-113) was done in 40 studies of 20 hypertensive patients. Eleven of 12 patients with a depressor response to angiotensin II blockade had significant renovascular or renal disease, and nine of 10 had renal vein renin measurements that lateralized to the abnormal kidney. In contrast, none of the patients without a depressor response had renovascular abnormalities. Plasma renin activity was usually high in responders to saralasin (18 ng/ml · h) when compared with nonresponders (0.5 ng/ml · h). In these studies a correlation between the fall in blood pressure and the rise in plasma renin activity during angiotensin II blockade was observed while renin was unchanged in the absence of depressor responses. In two renovascular renin-dependent hypertensive patients, treatment with diuretics induced severe hyperreninemia and a rise in blood pressure that was reversed by sodium loading.
Cases of Follicular Tonsillitis Due to Milk Infection
Authors: C. Grey-Edwards, W. D. Severn
Journal: BMJ (1897)

FOLLICULAR TONSILLITIS AND) MILK INFEJIION.[T O-339 it is the capsule, not the fibroid, which is vascular, and it is to the difficulty of adequate securing of the incised capsule that the principal risk of myomectomy is due.Both our patients made a good recovery, but in both the formation of a halmatoma was recognised.The remaining hysterectomy was done under rather pecu- liar circumstances:The subject was a rachitic dwarf on whom a Caesarean section had been done in I895.When she came to us she was about four months' pregnant, and finding her true conjugate to be only 4 inch, it was de- cided to let her go to term and then deliver her by abdominal section.She was thus delivered of a living boy, and the recurrence of pregnancy was, we thought, prevented by double ligature of both Fallopian tubes and incising them between the ligatures.The uterus was not removed at the time, as it was thought this would add greatly to the shock of the operation.Her recovery was unevenful and rapid.She left the hospital quite well at the end of a month.The child subsequently died at the age of 6 weeks of infantile syphilis.The mother continued to menstruate regularly, very profusely, and with great pair.The uterus remained im- perfectly involuted, and of course an abdominal organ, the neck only being felt per vaginam just above the narrow conjugate.It was found impossible to curette the uterus, and yet the girl was incapacitated by the monthly pain and haemorrhage.There was nothing unusual in the hysterectomy except that the anterior surface of the uterus was firmly adherent to the under surface of the peritoneum.Patient left the hos- pital for the convalescent cottage on the twenty-first day.Probably three causes continued to prevent perfect involution: I. Specific endometritis.2. Unnatural position of the uterus due to pelvic deformity.3. Adhe- sion of the scar on the anterior surface of the uterus to the peritoneum.
SKIN GRAFTING FOR THE RESTORATION OF THE EYELIDS.REPORT OF CASES.
Authors: OSCAR DODD
Journal: JAMA (1903)

Skin grafting for the restoration of the eyelids differs quite materially from that in other parts of the body. The prime objects in operating are cosmetic and restoration of function. To attain these the part must be freely movable and not differ in color and appearance markedly from the normal lid. We have also a field for operation which is movable and uneven, making the results more difficult to obtain. It is for these reasons that I think a discussion of the principles involved should be of benefit. The statements I shall make and conclusions I have reached are from my personal experience with these cases. Along with the successes I shall give an account of my failures, for I think I have learned more from these than from the cases where the results were satisfactory. I have used most of the forms of grafts described, the sliding graft, the
Effect of Measles Vaccination on Incidence of Measles in the Community
Authors: I. Sutherland, P. M. Fayers
Journal: BMJ (1971)

A study of the effect of measles vaccination on the incidence of the disease in eight separate areas of England and Wales was begun in 1966. It showed an inverse association between the proportion of children vaccinated and the incidence of measles in the area in the following year, but measles epidemics occurred in several of the areas in subsequent years, despite continuing vaccinations.Measles vaccination was introduced on a large scale in Britain in 1968. Analysis of the notification and vaccination statistics shows that the vaccination of about 10% of the child population (under 15 years) in 1968 sufficed to "replace" the measles epidemic which had been expected in the period October 1968 to September 1969 by a low incidence of the disease, typical of that in previous "interepidemic" years. Further, the effect of the vaccinations was to prevent the development of natural measles in susceptible unvaccinated children as well as in the vaccinated subjects. Thus the number of immune subjects in the community was increased by the vaccinations, but as a result there was a reduction in the number of subjects who acquired immunity from natural measles. These opposed results can therefore explain why vaccination may be effective in the community for only a year or two, though vaccination protects the individual for much longer.It is estimated that a continuing vaccination rate of 40 to 50% of the children born each year would be necessary to replace the regular biennial measles epidemics in Britain by a continuous endemic incidence, and might perhaps lead to the disappearance of the disease without a further major epidemic, but that a continuing vaccination rate of 80 to 90% of children born each year would then be necessary to prevent its reintroduction. The long-term control of measles by vaccination will thus probably prove more difficult than for any other infectious disease.
Plasma levels of IL-6 correlate with hemodynamic abnormalities in acute pancreatitis in rabbits
Authors: Zoltán Jambrik, Mariann Gyöngyösi, Péter Hegyi, László Czakó, Tamás Takács, András Farkas, Yvette Mándy, Csaba Góg, Dietmar Glogar, Miklós Csanády
Journal: Intensive Care Medicine (2002)
Serum <i>HER-2/neu</i> and Response to the Aromatase Inhibitor Letrozole Versus Tamoxifen
Authors: A. Lipton, S.M. Ali, K. Leitzel, L. Demers, H.A. Harvey, H.A. Chaudri-Ross, C. Brady, P. Wyld, W. Carney
Journal: Journal of Clinical Oncology (2003)

To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen.Five hundred sixty-two estrogen receptor-positive metastatic breast cancer patients were randomized to first-line hormone therapy with either letrozole or tamoxifen. An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu.For patients with normal serum HER-2/neu (70.5%), objective response rate (ORR; 39% in letrozole-treated patients v 26% in tamoxifen-treated patients; P =.008), clinical benefit (CB; 57% v 45%; P =.016), time to progression (TTP; median, 12.2 v 8.5 months; P =.0019), and time to treatment failure (TTF; median, 11.6 v 6.2 months; P =.0066) were significantly better in patients treated with letrozole. In the elevated HER-2/neu group (29.5%), there was no significant difference in ORR (17% in letrozole-treated patients v 13% in tamoxifen-treated patients; P =.45) or CB (33% v 26%; P =.31), but there was a strong trend in favor of a longer TTP with letrozole (median, 6.1 v 3.3 months; P =.0596) and a significantly longer TTF with letrozole (median, 6.0 v 3.2 months; P =.0418). Multivariate analysis revealed that elevated serum HER-2/neu was a negative predictor for ORR and TTP.Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen. Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB, there was a strong trend favoring longer TTP and significantly longer TTF with letrozole.
Dapsone suppresses human neutrophil superoxide production and elastase release in a calcium-dependent manner
Authors: T. Suda, Y. Suzuki, T. Matsui, T. Inoue, O. Niide, T. Yoshimaru, H. Suzuki, C. Ra, T. Ochiai
Journal: British Journal of Dermatology (2005)

Background Dapsone (4,4′‐diaminodiphenyl sulphone) is a powerful therapeutic tool in many skin diseases including neutrophilic dermatoses. The drug has an outstanding therapeutic efficacy against many skin diseases characterized by neutrophil‐rich infiltrates; however, mechanisms of its action are poorly understood. Objectives We investigated the effects of dapsone on respiratory and secretory functions of human neutrophils triggered by the chemotactic peptide N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine (fMLP), the physiological agonist C5a, and phorbol myristate acetate (PMA). Methods Human neutrophils were isolated from venous blood obtained from healthy donors. We detected extracellular production of superoxide (O2–) by cytochrome C reduction assay, and intracellular production of O2– by flow cytometry. Neutrophil elastase release was measured by the cleavage of the specific elastase substrate N‐methoxysuccinyl‐Ala‐Ala‐Pro‐Val‐p‐nitroanilide. Measurement of cytosolic free calcium concentration was performed using the calcium‐reactive fluorescence probe, Fluo‐3. Results Dapsone suppressed intra‐ and extracellular production of O2– and elastase release triggered by fMLP and C5a, but not by PMA. Both fMLP and C5a signalled the above pathways by inducing calcium influx, but PMA functions bypassed calcium influx. Dapsone was capable of antagonizing the induction of calcium influx. Conclusions These findings suggest that one mechanism of the anti‐inflammatory action of dapsone is inhibition of calcium‐dependent functions of neutrophils including release of tissue‐damaging oxidants and proteases in the affected skin.
Abstract LB-39: Sphingosine kinase activity is not required for tumor cell viability.
Authors: Holger Wesche, Matthew L. Brown, Timothy J. Carlson, Angela Coxon, Brendon Frank, Darin J. Gustin, Shawn Jeffries, Shyun Li, Yihong Li, Kurt Morgenstern, Kurt Morgenstern, Matthew Plant, Karen Rex, Joanna Schmidt, Shanling Shen, Nigel Walker, Dineli Wickramasinghe, Guifen Xu
Journal: Cancer Research (2013)

Abstract Sphingosine kinase activity is not required for tumor cell viability Holger Wesche, Matthew L. Brown, Timothy J. Carlson, Angela Coxon, Brendon Frank, Darin J. Gustin, Shawn Jeffries, Shyun Li, Yihong Li, Kurt Morgenstern, Matthew Plant, Karen Rex, Joanna Schmidt, Shanling Shen, Nigel Walker, Dineli Wickramasinghe, Mariwil Wong, Guifen Xu Contribution from the Departments of Oncology Research, Medicinal Chemistry, Molecular Structure and Characterization and Pharmacokinetics and Drug Metabolism, Amgen Inc., South San Francisco, 1120 Veterans Blvd., South San Francisco, Ca, 94080. Sphingosine kinases (SPHKs) are enzymes that phosphorylate the lipid sphingosine, leading to the formation of sphingosine-1-phosphate (S1P). In addition to the well established role of extracellular S1P as a mitogen and potent chemoattractant, SPHK activity has been postulated to be an important intracellular regulator of apoptosis. According to the proposed rheostat theory, SPHK activity shifts the intracellular balance from the pro-apoptotic sphingolipids ceramide and sphingosine to the mitogenic S1P, thereby determining the susceptibility of a cell to apoptotic stress. Despite numerous publications with supporting evidence, a clear experimental confirmation of the impact of this mechanism on tumor cell viability in vitro and in vivo has been hampered by the lack of suitable tool reagents. Utilizing a structure based design approach, we developed potent and specific SPHK1/2 inhibitors. These compounds completely inhibited intracellular S1P production in human cells and attenuated vascular permeability in mice, but did not lead to reduced tumor cell growth in vitro or in vivo. These results show that the SPHK rheostat does not play a major role in tumor cell viability, and that SPHK inhibition may not offer an advantage over S1P neutralization in the treatment of cancer. Citation Format: Holger Wesche, Matthew L. Brown, Timothy J. Carlson, Angela Coxon, Brendon Frank, Darin J. Gustin, Shawn Jeffries, Shyun Li, Yihong Li, Kurt Morgenstern, Kurt Morgenstern, Matthew Plant, Karen Rex, Joanna Schmidt, Shanling Shen, Nigel Walker, Dineli Wickramasinghe, Guifen Xu. Sphingosine kinase activity is not required for tumor cell viability. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-39. doi:10.1158/1538-7445.AM2013-LB-39
Small early tubular adenomas and mixed colonic polyps found on screening flexible sigmoidoscopy do not predict proximal neoplasia in males
Authors: Nadeem Ullah, Kashif Qureshi, James Hatfield, Paula Sochacki, Doina David, Hassan Albataineh, Luis Mejia, Chaya Kenkre, Michael Lawson, Martin Tobi
Journal: Clinical Gastroenterology and Hepatology (2004)
Who Benefits From Medical Savings Accounts?
Authors: Eugene Guazzo
Journal: JAMA (1996)

To the Editor.  —Although the objective of the study by Dr Keeler and colleagues 1 was to understand the effects of medical savings accounts (MSAs) on health care costs, an equally important feature of this legislation on health care is that it puts the patient back in charge of his or her own money. This gives the patient some control of the medical system and allows the patient to be an independent shopper, somewhat free of physician, insurance company, and politician constraints. In other words, it is similar to the way medicine used to be some years ago, from an economic point of view.  From a marketing point of view, we have a much more sophisticated patient today than was the situation a generation ago. The old adage that the doctor knows best would be tempered with the MSA system and informed choice.  Ultimately, this bodes well for the patient
DJ-1 can inhibit microtubule associated protein 1 B formed aggregates
Authors: Zhiquan Wang, Yu Zhang, Shi Zhang, Qianqian Guo, Yuyan Tan, Xinyi Wang, Ran Xiong, Jianqing Ding, Shengdi Chen
Journal: Molecular Neurodegeneration (2011)

Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD.We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis.Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD).
The Epidemiology of Food Sensitization-Associated Eczema in Infancy in HealthNuts, a Population-based Study
Authors: S.C. Dharmage, P.E. Martin, N.J. Osborne, J.J. Koplin, L.C. Gurrin, A. Ponsonby, M.L. Tang, M.C. Matheson, A.J. Lowe, T. Dang, T. Tan, D. Anderson, L. Thiele, M. Sutherland, L. Miles, M. Wake, K.J. Allen
Journal: Journal of Allergy and Clinical Immunology (2011)
Early antenatal diagnosis of small open spina bifida lesions.
Authors: D J Brock, C Gosden
Journal: BMJ (1977)

dialysis may not be readily accomplished in some patients who have had recent abdominal surgery, multiple abdominal fistulas, or extreme adhesive peritonitis.The technique described here provides a good compromise, in that those patients with acute renal failure may undergo early haemodialysis with a shunt.The vasculature which is enlarged by the fast flow of the shunt may then be converted to a fistula which can be used immediately for haemodialysis.