tbuckley/cabot-search huggingface dataset:
Placebo run in periods
Authors: P. Sedgwick
Journal: BMJ (2012)

Tri-o-cresyl phosphate (TOCP) and triphenyl phosphite (TPP) are known to be neurotoxic in several species. In a previous study, we found that the subcutaneous administration of the compounds may result in toxicological effects which are prolonged in comparison to administration by other routes. In order to test the hypothesis that slow absorption from the injection site could account for our results, we monitored the disappearance of either compound from the injection site using in vivo 31P nuclear magnetic resonance (NMR). In addition, the test samples and some potential metabolites were examined in vitro with NMR. The disappearance of equimolar doses of subcutaneously injected TOCP (1187 mg/kg) and TPP (1000 mg/kg) from the injection site, with time, showed a biphasic pattern. The first phase took place within a few hours, while the second phase was very slow, with a half-life of about 2 weeks for both compounds. These results may account for the prolonged neuropathy target enzyme inhibition and explain the delayed neurotoxicity produced by subcutaneous injection of TOCP and TPP. Two animals given TPP exhibited an atypical pattern, in that the TPP apparently converted to diphenyl phosphonic acid within several hours of injection. In these hens, this phenomenon was accompanied by acute lethality. The conversion to diphenyl phosphonic acid also took place when the TPP was placed in an aqueous solution in vitro. Diphenyl phosphonic acid may play a role in the unique toxicity of TPP.
Advances in Mycobacterium siderophore-based drug discovery
Authors: Jun-li He, Jian-ping Xie
Journal: Acta Pharmaceutica Sinica B (2011)

Tuberculosis remains a public health threat of global proportions. Iron is a scarce resource indispensable to both host and pathogen during infection with Mycobacterium tuberculosis, the causative agent of tuberculosis. Siderophores are critical molecules for iron acquisition under iron-limiting conditions and, as a very efficient pathogen, M. tuberculosis has evolved elaborate siderophores knowledge of which is being intensively translated into clinical practice. This paper summarizes the structures, types and physiological functions of Mycobacterium siderophores with emphasis on siderophore-inspired design of drugs and drug delivery vehicles.
No Magic Bullet: A Social History of Venereal Disease in the United States Since 1880
Authors: D. M. Connors
Journal: JAMA (1986)

The important and timely conclusion reached in Allan M. Brandt's No Magic Bullet is that efforts to influence individual behavior as the primary means of controlling venereal disease historically have by and large been failures.  When the campaign against venereal disease was a campaign to curtail promiscuity, appealing to the sanctity of the family, emphasizing moral values, and promoting programs designed to sublimate the sexual urge, there was negligible effect on the incidence of venereal infection. Even where prostitution was eliminated, there was little reduction in venereal infection because of the large numbers of amateurs in the field. Medical means such as providing easy access to prophylaxis and treatment, coupled with epidemiologic case-finding techniques, have been extremely successful. Witness the near disappearance of syphilis and gonorrhea in the 1950s through the momentum established during World War II after the advent of penicillin.   No Magic Bullet traces the social attitudes and
Nonlinear relation between Vmax and INa in canine cardiac Purkinje cells.
Authors: M F Sheets, D A Hanck, H A Fozzard
Journal: Circulation Research (1988)

We studied the relation of the maximal upstroke velocity (Vmax) of action potentials to the peak sodium current (INa) under voltage clamp in single, internally perfused, canine cardiac Purkinje cells under conditions that ensured membrane action potentials due only to INa. Three different methods of altering sodium channel availability were investigated: voltage-dependent inactivation, tetrodotoxin (TTX) block, and use-dependent block by quinidine. Under all three conditions, the relation of Vmax to INa was nonlinear, and no relation was found that would allow prediction of INa results from Vmax measurements. With voltage-dependent inactivation or TTX block, sodium channel availability measured by Vmax was reduced less than availability measured by peak INa, so that Vmax overestimated sodium channel availability. This overestimation of sodium channel availability by Vmax could be attributed to greater sodium channel mobilization during the slowed action potential upstrokes. The overestimation varied with experimental temperature as a consequence of changes in sodium channel kinetics. Vmax also overestimated sodium channel availability during TTX exposure so that the Kd for TTX block was 4.5 micron from Vmax measurements but only 1.6 microM from INa measurements. Use-dependent block of INa by quinidine had a striking voltage-dependent component under voltage clamp that could not be appreciated from action potentials. Consequently, block could be underestimated or overestimated by Vmax measurements. We conclude that Vmax measurements represent a convenient index for INa, but Vmax is not a reliable method for quantitative studies of sodium channel behavior.
Milk Supervision and Certification by County Societies.
Authors: C. G. Parnall
Journal: JAMA (1907)

Jackson, Mich., Aug. 28. 1907. <h3>To the Editor:</h3> —Enclosed find our scheme for obtaining pure milk, which is self-explanatory. As you will notice, our plan is somewhat different from the usual one of certifying the product from only one dairy. Any dairyman who will comply with our rules and furnish a product meeting standard requirements as to bacterial content and food elements may have our certification. The scheme has already secured good results. [The work to which Dr. Parnall calls attention is being done through a committee appointed by the Jackson County (Mich.) Medical Society. A circular and a card of application for certification are sent to the dairymen. The former embodies the most important recommendations and measures for producing clean milk, requiring the dairyman to agree to inspection by the committee and to abide by its rules and regulations. Any case of communicable disease occurring in the household of
A1.73 Relationship between expression of synovial B cell survival factors and clinical response to rituximab treatment in rheumatoid arthritis
Authors: Rogier M Thurlings, Marie Boumans, W J de Jager, Koen Vos, Daisy Marie van Westing, Lisa G van Baarsen, Danielle M Gerlag, B Prakken, Paul P Tak, Paul P Tak
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Rituximab aims to deplete CD20 positive B cells and exerts a significant and often long-lasting clinical effect in a subset of patients with rheumatoid arthritis (RA). The extent of B cell depletion in the inflammatory tissues after rituximab varies between patients and persistence of plasma cells and plasma cell products is associated with clinical non-response. This suggests rituximab may fail to deplete pathogenic B cells. We investigated whether this might be explained by differential expression of B cell survival factors in the inflamed synovial tissue of RA patients. <h3>Material and Methods</h3> Twenty-four RA patients underwent an arthroscopic synovial biopsy before, 1 month after and 4 months after treatment with rituximab. Treatment was given via two infusions (1,000 mg on day 1 and 15), both without methylprednisolon premedication to be able to study specific biological effects of rituximab. Clinical response was defined as a response according to the European League Against Rheumatism (EULAR) criteria at week 24. Peripheral blood and synovial tissue were analysed for expression and levels of B cell survival factors; BLyS, APRIL, IL-1β, IL6, BLyS, VCAM, ICAM, IFNα, CXCL12 and BLIMP1. Correlation between baseline expression and changes in B cell survival factors and clinical response were calculated using logistic regression analysis. <h3>Results</h3> We found no significant correlation between baseline expression level of synovial B cell survival factors and clinical response to treatment. After treatment, the expression levels of BLyS, APRIL, IL-1β, IL6, ICAM and BLIMP1 were unaltered. The expression of IFNα and VCAM decreased after treatment, of which VCAM within one month (<i>P</i> = 0.035, <i>P</i> = 0.022 and <i>P</i> = 0.039, respectively). In contrast, expression of CXCL-12 increased after treatment (<i>P</i> = 0.046). In clinical responders VCAM expression decreased further between 1 and 4 months after treatment, although a statistical significant difference with non-responders could not be detected. <h3>Conclusions</h3> Clinical non-response to rituximab is not associated with a higher baseline expression of B cell survival factors in the inflamed synovial tissue of RA patients. However, the persistent expression of survival factors independent of the extent of B cell depletion may promote the persistence of pathogenic B cell subsets in clinical non-responders to treatment.
Regulation of angiotensin II in rat adrenal gland.
Authors: A Husain, P DeSilva, R C Speth, F M Bumpus
Journal: Circulation Research (1987)

Levels of angiotensin II immunoreactivity in the rat adrenal gland are over one hundredfold higher than those in plasma. It is unclear, however, whether the major source of adrenal angiotensin II immunoreactivity is intracellular synthesis by a local renin-angiotensin system, uptake by angiotensin II receptors, or both. Our studies show that angiotensin II immunoreactivity in the adrenal gland is predominantly attributable to angiotensin II (greater than 75%). Angiotensin III (16%) and other angiotensin II fragments are also present. The majority of angiotensin II immunoreactivity (73%), renin activity (73%), and angiotensin II receptor binding activity (66%) in the adrenal gland is located in the capsular glomerulosa cell layers. Dehydration produced by 2% NaCl imbibition decreased these activities in the capsular-glomerulosa. In the fasciculata-medullary regions of the adrenal gland, dehydration decreased renin activity but not angiotensin II immunoreactivity or angiotensin II receptor binding activity. Combined data from control and dehydrated rats showed a close correlation of the capsular-glomerulosa angiotensin II immunoreactivity with angiotensin II receptor binding activity (r = 0.94, p less than 0.001) and a weaker, nonsignificant correlation with renin activity (r = 0.66, p less than 0.1). In the fasciculata-medullary cell layers, no significant correlations were found between angiotensin II immunoreactivity and either renin or angiotensin II receptor binding activity. These data demonstrate that functionally distinct layers of the rat adrenal gland differentially regulate angiotensin II receptors and the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 263: MYC enforces overexpression of EZH2 in early prostatic neoplasia via transcriptional and posttranscriptional mechanisms
Authors: Cheryl M. Koh, Tsuyoshi Iwata, Qizhi Zheng, Carlise Bethel, Srinivasan Yegnasubramanian, Angelo M. De Marzo
Journal: Cancer Research (2011)

Abstract EZH2 is part of the PRC2 polycomb repressive complex that is overexpressed in multiple cancer types and has been implicated in prostate cancer initiation and progression. Here we identify EZH2 as a target of the MYC oncogene in prostate cancer and show that MYC coordinately regulates EZH2 through transcriptional and post-transcriptional means. Although prior studies in prostate cancer revealed a number of possible mechanisms of EZH2 upregulation, these changes cannot account for the overexpression of EZH2 in many primary prostate cancers, nor in most cases of high grade PIN. We report that upregulation of MYC in the mouse prostate results in overexpression of EZH2 mRNA and protein which coincides with reductions in miR-26a and miR-26b, known regulators of EZH2 in some non-prostate cell types, albeit not in others. Further, in human prostate cancer cells, MYC negatively regulates miR-26a and miR-26b via direct binding to their parental Pol II gene promoters, and forced overexpression of miR-26a and miR-26b in prostate cancer cells results in decreased EZH2 levels and suppressed proliferation. In human clinical samples, miR-26a and miR-26b are downregulated in most prostate cancers. In a novel mechanism of EZH2 mRNA upregulation, we find that MYC binds directly to and activates the transcription of the EZH2 promoter. These results link two major pathways in prostate cancer by providing two additional and complementary MYC-regulated mechanisms by which EZH2 upregulation occurs and is enforced during prostatic carcinogenesis. Further, the results implicate EZH2-driven mechanisms by which MYC may stimulate prostate tumor initiation and disease progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 263. doi:10.1158/1538-7445.AM2011-263
The Present State of Light Guide Type Fibergastroscope and Characteristics of Gastric Biopsy under Direct Vision
Authors: T. Takemoto, K. Tsuneoka, I. Oi, T. Fujita, T. Kondo
Journal: Endoscopy (1970)

Outline of the abilities and characteristics of light guide type FGS with an extremely high properties as the result of frequent improvement since 1963 was presented along with the characteristics of gastric biopsy under direct vision through FGS for biopsy.
Limbal Allograft, Amniotic Membrane Transplantation, and Intraoperative Mitomycin C for Recurrent Pterygium
Authors: Takashi Miyai, Ryuhei Hara, Ryohei Nejima, Kazunori Miyata, Takaharu Yonemura, Shiro Amano
Journal: Ophthalmology (2005)
STUDIES ON LOW DOSE CHLOROQUINE THERAPY AND THE ACTION OF CHLOROQUINE IN SYMPTOMATIC PORPHYRIA
Authors: J. J. F. TALJAARD, B. C. SHANLEY, E. G. STEWART-WYNNE, W. M. DEPPE, S. M. JOUBERT
Journal: British Journal of Dermatology (1972)

Journal Article STUDIES ON LOW DOSE CHLOROQUINE THERAPY AND THE ACTION OF CHLOROQUINE IN SYMPTOMATIC PORPHYRIA Get access J. J. F. TALJAARD, J. J. F. TALJAARD Departments of Chemical Pathology, Faculty of Medicine, University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic Google Scholar B. C. SHANLEY, B. C. SHANLEY Departments of Chemical Pathology, Faculty of Medicine, University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic Google Scholar E. G. STEWART‐WYNNE, E. G. STEWART‐WYNNE Departments of Chemical Medicine, Faculty of Medicine, University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic Google Scholar W. M. DEPPE, W. M. DEPPE Departments of Chemical Pathology, Faculty of Medicine, University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic Google Scholar S. M. JOUBERT S. M. JOUBERT Departments of Chemical Pathology, Faculty of Medicine, University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 87, Issue 3, 1 September 1972, Pages 261–269, https://doi.org/10.1111/j.1365-2133.1972.tb00316.x Published: 01 September 1972 Article history Accepted: 14 March 1972 Published: 01 September 1972
Melancholia and Depression: From Hippocratic Times to Modern Times
Authors: George H. Pollock
Journal: JAMA (1987)

Stanley W. Jackson, MD, is a professor of psychiatry and the history of medicine at the Yale University School of Medicine. In addition, he is a psychoanalyst, a practicing clinician who brings together his skills, knowledge, and wisdom in this excellent contribution. In<i>Melancholia and Depression</i>he covers the subject in depth and breadth and integrates issues, questions, and topics that relate to but are not solely concerned with depression and melancholia. Jackson's presentation is the history of "a group of closely related syndromes." Indeed it is, and he clearly and interestingly presents a fascinating account based on 2500 years of medical writings on this subject. Utilizing this sweeping panorama, he concludes that despite variations in the descriptions of these clinical disorders, "there have been both a remarkable consistency and a remarkable coherence in the basic cluster of symptoms." In addition, Jackson surveys the various theoretical explanations of these affective
Increased sensitivity to nitrazepam in old age.
Authors: C M Castleden, C F George, D Marcer, C Hallett
Journal: BMJ (1977)

The effects of a single 10 mg oral dose of nitrazepam were compared with those of a placebo in healthy young and old people. Both the young and the elderly slept better on three successive nights after nitrazepam but they felt less awake at 12 and 36 hours (P less than 0-01). Elderly people made significantly more mistakes in a psychomotor test than did the young, despite similar plasma concentrations of nitrazepam and half lives in the two groups. This difference in response to psychomotor testing is probably explained by an increased sensitivity of the ageing brain to the action of nitrazepam.
Editorial: The burn-prone society
Authors: F. D. Moore
Journal: JAMA (1975)

The care of a severely burned patient imposes a remarkable requirement on the supporting community for nurses, physicians, allied health personnel, special care facilities, and laboratory back-up as well as a large share of hospital beddays. Many hospitals that receive burn cases only occasionally have, quite wisely, adopted the policy of early transfer to units more suitably equipped by facilities and experience. Once the early respiratory threat has abated, and the early fluid therapy is judged satisfactory for transport, the patient is safely transportable. Far better to transport the patient to a burn center early in his course, rather than "hanging on" until sepsis and failure of skin grafting forces transfer. Wherever definitive treatment is given, the patient faces long months of intense physical suffering with the outcome long in doubt. Although many details of care have been improved in the past 25 years and rehabilitation accelerated for survivors, there
Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia
Authors: Bipin N. Savani, Katayoun Rezvani, Stephan Mielke, Aldemar Montero, Roger Kurlander, Charles S. Carter, Susan Leitman, Elizabeth J. Read, Richard Childs, A. John Barrett
Journal: Blood (2005)
OSTEOMYELITIS OF THE FRONTAL BONE AS A COMPLICATION OF FRONTAL SINUSITIS
Authors: ALBERT E. BULSON
Journal: JAMA (1926)

Osteomyelitis of the frontal bone as a complication of frontal sinus suppuration is a relatively rare condition. A search of much of the American and European literature for thirty years back discloses reports of a total of fifty-five cases, in thirty-seven of which death occurred. The nature and the etiology of some of those cases may be questioned, owing to the incompleteness of the reports. Out of this total number of fifty-five cases, twenty-eight may be classed as occurring as a complication of chronic suppuration of the frontal sinus, twenty-one of which resulted in death and seven in recovery. In only eight of these twenty-eight chronic cases, in all of which operation was performed, was osteomyelitis discovered at the time of the first operation; four of the eight patients died and four recovered. In twenty cases, the osteomyelitis developed subsequent to operative attention for the sinusitis, and subsequently required operation
THE EFFECT OF AN INFUSION OF HYPERONCOTIC ALBUMIN ON THE EXCRETION OF WATER AND SOLUTES 12
Authors: R. G. Petersdorf, L. G. Welt
Journal: Journal of Clinical Investigation (1953)

The origin of the diabetes insipidus appeared to be post- encephalitic in F. S. and due to reticuloendotheliosis in J. V.Both had an inability to concentrate the urine al- though the volumes in J. V. were not tremendous which may have been related to a coexisting mild hypothyroidism.Patient F. S. had the typical response of diabetes insipidus to the Hickey-Hare test (6).This was not per- formed on subject J. V.It is, of course, impossible to state whether the diabetes insipidus
Modification of Adenoviral Vectors With Polyethylene Glycol Modulates In Vivo Tissue Tropism and Gene Expression
Authors: Sean E Hofherr, Elena V Shashkova, Eric A Weaver, Reeti Khare, Michael A Barry
Journal: Molecular Therapy (2008)

Polyethylene glycol (PEG) is a hydrophilic polymer that has been used to coat adenoviral (Ad) vectors to improve their pharmacology. To analyze the effects of PEG on Ad5 tropism, Ad5 was covalently modified with different sizes of PEG and in vitro and in vivo transduction was analyzed. All tested PEGs ablated in vitro transduction. When protein C (PC) and factors VII, IX, and X were added, only factors IX and X increased transduction by the PEGylated vectors with the largest effect by X. Inactivation of these factors with warfarin drastically reduced liver transduction in mice by the PEGylated vectors after intravenous (IV) injection. Ad5 conjugated with 5 kd PEG maintained normal liver transduction while conjugation with larger 20 and 35 kd PEGs significantly reduced liver transduction. When intraperitoneal (IP) injection was tested, Ad transduced the peritoneum efficiently with only low level liver transduction. When Ad5 was modified with 5 kd PEG, peritoneal transduction was reduced and the virus preferentially transduced the liver. These data demonstrate the effects of different sizes of PEG on in vivo Ad tropism and suggest that this approach may be useful in retargeting and detargeting Ad in vivo. Polyethylene glycol (PEG) is a hydrophilic polymer that has been used to coat adenoviral (Ad) vectors to improve their pharmacology. To analyze the effects of PEG on Ad5 tropism, Ad5 was covalently modified with different sizes of PEG and in vitro and in vivo transduction was analyzed. All tested PEGs ablated in vitro transduction. When protein C (PC) and factors VII, IX, and X were added, only factors IX and X increased transduction by the PEGylated vectors with the largest effect by X. Inactivation of these factors with warfarin drastically reduced liver transduction in mice by the PEGylated vectors after intravenous (IV) injection. Ad5 conjugated with 5 kd PEG maintained normal liver transduction while conjugation with larger 20 and 35 kd PEGs significantly reduced liver transduction. When intraperitoneal (IP) injection was tested, Ad transduced the peritoneum efficiently with only low level liver transduction. When Ad5 was modified with 5 kd PEG, peritoneal transduction was reduced and the virus preferentially transduced the liver. These data demonstrate the effects of different sizes of PEG on in vivo Ad tropism and suggest that this approach may be useful in retargeting and detargeting Ad in vivo.