tbuckley/cabot-search huggingface dataset:
Methyl Thiouracil and Anginal Pains
Authors: W. N. Rogers
Journal: BMJ (1951)

Forty-two kinds of mammals and six kinds of reptiles were identified. The extinct and extralimital fauna is believed to date from a time when climatic conditions resembled those of southeastern Wyoming and adjacent Colorado; vegetation probably consisted of sagebrush grasrassland with few or no trees present. The evidence suggests degeneration of these conditions directly to those of historic times without an intervening arid, warm Altithermal period.--H.C.W.S
PROLONGED RETENTION OF URINE DUE TO AN ANTIDEPRESSANT DRUG
Authors: G. F. J. GODDARD
Journal: American Journal of Psychiatry (1962)

A case is described of urinary retention lasting 27 days after 15 days' treatment with amitriptyline hydrochloride (Tryptizol). The interesting features are 1) the long duration of the condition after the drug was stopped and 2) the failure of a cholinergic drug (carbachol) to counteract the anti-cholinergic activity of Tryptizol. The case demonstrates the necessity for daily examination for urinary retention of patients receiving amitriptyline HCL, particularly of cases who cannot be expected to make spontaneous complaint of urinary symptoms, due to dementia, depression or apathy.
Neuropsychological assessment for detecting adverse effects of volatile organic compounds on the central nervous system.
Authors: K I Bolla
Journal: Environmental Health Perspectives (1991)

Because there are no direct biological markers for the substances implicated in indoor air exposure, it is impossible to directly measure if an individual or group of individuals has been exposed to a potentially neurotoxic substance in the workplace. Behavioral changes may be the earliest and only manifestation of central nervous system (CNS) effects and are often too subtle to be revealed by routine physical or neurological examination. Neuropsychological techniques are sensitive to subtle behavioral/cognitive changes that can result from exposure to neurotoxins. These techniques consist of oral and written tests that are administered by a trained examiner on a one-to-one basis. In general, a wide variety of cognitive domains are evaluated. The typical battery generally includes assessing orientation, attention, intelligence, language, visual memory, verbal memory, perception, visuoconstruction, simple motor speed, psychomotor speed, and mood. As with most assessment techniques, the neuropsychological methods have limitations. One major drawback is the availability of appropriate norms that are used to compare the results of a specific individual. Because these tasks are greatly affected by age, intelligence, and in some instances sex, the availability of appropriate norms is mandatory to determine if the CNS has been effected. Although neuropsychological tests are sensitive to the presence of CNS involvement, they are not specific. Patterns of performance seen with specific instances of neurotoxic exposure may also be seen with a number of other diseases of the CNS such as dementia, cerebrovascular disease, hydrocephalus, or normal aging. In addition, neuropsychiatric symptoms such as anxiety and/or depression are often manifested as cognitive difficulties that will mimic the cognitive dysfunction seen with toxicity of the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)
Recognition of Mental Distress and Diagnosis of Mental Disorder in Primary Care
Authors: Stephen F. Jencks
Journal: JAMA (1985)

Data from the National Ambulatory Medical Care Survey show that the majority of psychotropic drugs and "psychotherapy/therapeutic listening" provided to adults in office-based primary care are given in visits during which no diagnosis of mental disorder is recorded. This finding is not explained either by a general tendency of surveyed physicians to record drug treatment without an appropriate diagnosis or by management of specific nonmental disorders with mental treatments. Patients who receive treatment without diagnosis tend to be older, established patients with established diagnoses who see the physician for a shorter visit and are more likely to have a follow-up appointment. The data do not provide evidence as to whether mental treatment without mental diagnosis results from inadequacies in the current diagnostic system, inadequacies of physician knowledge and skills, or other factors. Further clarification of this issue will require new research models.
Fas-Mediated Apoptosis in Adriamycin-Induced Cardiomyopathy in Rats
Authors: Tsuneyuki Nakamura, Yoshimichi Ueda, Yang Juan, Shogo Katsuda, Hiroaki Takahashi, Eikan Koh
Journal: Circulation (2000)

Background —The precise molecular mechanism of Adriamycin-induced cardiomyopathy (ADR-CM) is still unknown. We address the demonstration of apoptotic myocardial cell death and the apoptosis-inducing molecules in ADR-CM induced in rats. Methods and Results —Until 8 weeks after the first administration of ADR, there was no increase in the number of labeled cells by terminal deoxynucleotidyl transferase assay (TUNEL method). Apoptotic indices increased significantly at weeks 9 and 10 in hearts of the ADR-treated group but not in those of the control group (0.42±0.12% versus 0.10±0.02% and 0.86±0.11% versus 0.09±0.04% at weeks 9 and 10, respectively). DNA ladder formation was also observed in the myocardial tissues during the late stages of the ADR-CM of rats. There was no significant difference in expression of p53 gene between the ADR group and the control group at either the message or the protein level. An overexpression of Fas antigen was shown in myocardial cells of ADR-treated hearts at weeks 9 and 10 by both Western blotting and immunofluorescent staining. Furthermore, we confirmed that neutralization of anti–Fas ligand antibody inhibited ADR-induced apoptosis. Conclusions —Apoptotic cell death was observed in the hearts of ADR-CM rats, and the number of apoptotic myocardial cells increased with the deterioration of morphological findings and cardiac function, indicating that apoptosis may be an important mechanism of loss of myocardial cells and cardiac dysfunction in ADR-CM. Apoptosis in ADR-CM rats is not p53-dependent but rather is executed through a Fas-mediated pathway.
In vitro action of bombesin on amylase secretion, membrane potential, and membrane resistance in rat and mouse pancreatic acinar cells. A comparison with other secretagogues.
Authors: N Iwatsuki, O H Petersen
Journal: Journal of Clinical Investigation (1978)

Bombesin caused depolarization of rat or mouse pancreatic acinar cell membrane, reduction of membrane resistance, and a steep rise in amylase output from superfused pancreatic fragments. These effects were similar to those previously described for acetylcholine, cholecystokinin, and gastrin. The dose-response curves for these three effects of bombesin were very similar, with effects being detectable at concentrations of about 30 pM and maximal effects at about 10 nM. The equilibrium potential for the membrane action of bombesin, i.e., the membrane potential at which bombesin did not cause any change in membrane potential, was -16 mV. Similar values for equilibrium potential were obtained with acetylcholine, caerulein and pentagastrin. Bombesin in the higher dose range (10 nM) caused electrical uncoupling of acinar cells within an acinus, i.e., a marked increase in junctional membrane resistance. Similar uncoupling effects were observed after acetylcholine, caerulein, and pentagastrin stimulation. In conclusion, bombesin acts on the pancreatic acinar plasma membrane in exactly the same way as acetylcholine and cholecystokinin-pancreozymin. The electrical uncoupling caused by stimulation is evidence for an increase in cytosol free calcium ion concentration.
In vivo transgenic bioassays and assessment of the carcinogenic potential of pharmaceuticals.
Authors: J F Contrera, J J DeGeorge
Journal: Environmental Health Perspectives (1998)

There is general agreement in the scientific community on the need to improve carcinogenicity testing and the assessment of human carcinogenic risk and to incorporate more information on mechanisms and modes of action into the risk assessment process. Advances in molecular biology have identified a growing number of genes such as protooncogenes and tumor-suppressor genes that are highly conserved across species and are associated with a wide variety of human and animal cancers. In vivo transgenic rodent models incorporating such mechanisms are used to identify mechanisms involved in tumor formation and as selective tests for carcinogens. Transgenic methods can be considered an extension of genetic manipulation by selective breeding, which long has been employed in science and agriculture. The use of two rodent species in carcinogenicity testing is especially important for identifying transspecies carcinogens. The capacity of a substance to induce neoplasia across species suggests that the mechanism(s) involved in the induction of the neoplasia are conserved and therefore may have significance for humans. Based on available information there is sufficient experience with some in vivo transgenic rodent carcinogenicity models to support their application as complementary second species studies in conjunction with a single 2-year rodent carcinogenicity study. The optional substitution of a second 2-year rodent carcinogenicity study with an alternative study such as an in vivo transgenic carcinogenicity study is part of the International Conference on Harmonization guidance S1B: Testing for Carcinogenicity of Pharmaceuticals. This guidance is intended to be flexible enough to accommodate a wide range of possible carcinogenicity assessment models currently under consideration or models that may be developed in the future. The use of an in vivo transgenic mouse model in place of a second 2-year mouse study will improve the assessment of carcinogenic risk by contributing insights into the mechanisms of tumorigenesis and potential human relevance not available from a standard 2-year bioassay. It is envisioned that this will stimulate the further development of more efficient and relevant methods for identifying and assessing potential human carcinogenic risk, which will benefit public health.
New Routes to Goals of Prostate Cancer Research
Authors: Phil Gunby
Journal: JAMA (1997)

AS 1997 gets under way, prostate cancer investigators are trying to narrow a search in a region of 80 to 300 or so genes on the long arm of chromosome 1. At the same time, many of these researchers are seeking to broaden prostate cancer research through a new teleconferencing network. The chromosome searchers' goal is to pinpoint the location of a gene that, when it undergoes mutation, appears to increase a man's risk of developing a prostatic tumor in his 9th decade from about 15% to close to 90%. The telecommunicators' goal, in the words of Alan W. Partin, MD, PhD, Johns Hopkins Medical Institutions, Baltimore, Md, includes "addition of numerous sites around the country where prostate cancer research is being performed." <h3>Chromosome Study</h3> For the chromosome explorers, "strong evidence of a major prostate cancer susceptibility locus" (<i>Science</i>. 1996;274:1371-1374) is apparent from work at Johns Hopkins' Brady Urological Institute;
Accounting for taste
Authors: Amy Maxmen
Journal: The Journal of Experimental Medicine (2009)

With palates so delicate they put food critics to shame, T cell receptors distinguish tiny bumps in molecular shape, report Archbold et al. on page 209.






Figure 1

A conformational change allows T cell receptors to attach more firmly to an EBV peptide bound to HLAB*4405.




Although close members of the HLA-B44 family differ by a single amino acid, they aren't interchangeable. Mismatches of HLA-B*4402 and B*4403 lead to transplant rejection. And people with B*4405 generate stronger CD8+ T cell responses against Epstein-Barr virus (EBV)than do people with either B*4402 or B*4403. Few HLA molecules have been crystallized along with their corresponding T cell receptors (TCR), so the physical basis for picky T cell preference is largely unknown.

Archbold et al. now show how just one amino acid, buried within the antigen-binding region of B*4402, B*4403, and B*4405, indirectly alters T cell recognition. Using an EBV epitope as a model, the authors found that B*4405 allowed the peptide more room to wiggle at the binding site than did B*4402 or B*4403. And that extra flexibility allowed the TCR to further change the peptide shape upon binding, allowing it to grasp onto the peptide-HLA complex more tenaciously. As a result, T cells had a 10-fold higher affinity for the peptide bound to B*4405 than to the other B44 alleles.

Therefore it wasn't the HLA polymorphism itself that altered the T cell recognition, but rather the slight shape change it caused in the bound peptide. This indirect effect probably extends to other “micropolymorphic” HLA alleles beyond the B44 family, say the authors.
A novel system for efficient gene transfer into primary human hepatocytes via cell-permeable hepatitis B virus-like particle
Authors: Boerries Brandenburg, Lars Stockl, Cindy Gutzeit, Martin Roos, Joachim Lupberger, Ruth Schwartlander, Hans Gelderblom, Igor M. Sauer, Peter Hans Hofschneider, Eberhard Hildt
Journal: Hepatology (2005)

Protein transduction domains (PTDs) have been used to deliver a variety of biologically active cargo across cellular membranes. However the potential of PTDs to mediate transport of nanoparticular structures into the cytoplasm bypassing the endosomal compartment remains unclear. Cell-permeable virus-like particles (VLPs) harboring a marker gene based on hepatitis B virus nucleocaspids were established. Cell permeability was achieved by fusion with translocation motif (TLM)-PTD. Electron and confocal microscopy revealed that these VLPs translocate as complete particles across the plasma membrane and transverse the cytoplasm toward the nucleus. Inhibition of endocytosis did not affect translocation of these VLPs into the cytoplasm. Based on these particles, a gene transfer system was developed. To this end the particles were loaded with DNA-encoding small hepatitis B virus surface antigen (SHBs) or green fluorescence protein (eGFP) that served as marker genes. Although the DNA-packaging efficiency was very low, applying the appropriate number of VLPs to primary human hepatocytes a gene transfer efficiency of approximately 95% was observed. In conclusion, the TLM-PTD has the potential to mediate efficient transfer of assembled particles and its cargo, nucleic acids, into primary human hepatocytes. This provides the basis for development of novel transducible therapeutic or diagnostic particles. (HEPATOLOGY 2005;42:1300–1309.)
Abstract 5658: Quercetin induces tumor-selective apoptosis involving downregulation of Mcl-1 and activation of Bax
Authors: Senping Cheng, Gang Chen, Young-ok Son, Jia Luo, Xianglin Shi
Journal: Cancer Research (2010)

Abstract Quercetin is a promising antitumor agent that induces apoptosis in a variety of tumor cells. However, the underlying mechanisms how this drug works are unclear. Here we report that administration of quercetin in human leukemia cells resulted in marked release of cytochrome c, cleavage of caspase 8, 9, 7 and 3, and apoptosis. Pronounced apoptosis was also noted in diverse primary leukemia cells but not in normal blood peripheral mononuclear cells. These events were accompanied by Mcl-1 down-regulation, most likely through a rapid dephosphorylation of translation initiation factor eIF4E. Following quercetin, Bax protein underwent conformational change and mitochondrial translocation which triggered cytochrome c release. Knockdown Bax by siRNA partially reversed querctin-induced apoptosis. Essentially, knockout of Bax completely abrogated the activation of caspase 9, 7 and 3, PARP cleavage and apoptosis, indicating that Bax is primarily required for quercetin lethality. Ectopic expression of Mcl-1 attenuated quercetin-mediated Bax activation, translocation and cell death. Conversely, interruption of Mcl-1 by siRNA enhanced Bax activation and translocation, as well as lethality induced by quercetin. However, the absence of Bax had no effect on quercetin-mediated Mcl-1 down-regulation. These results suggest that Mcl-1 may operate upstream of Bax. Finally, addition of quercetin increased Bid cleavage. The caspase 8 specific inhibitor prevented Bid cleavage, Bax activation, and subsequent caspase 3 processing. Knockout of Bax had no effect on the processing of caspase 8 and Bid. These observations indicate that Bax activation is also mediated by caspase 8 dependent Bid cleavage upon quercetin treatment. Collectively, these findings demonstrate that quercetin mediates Mcl-1 down-regulation and Bid cleavage which potentiate Bax activation and mitochondrial translocation, events that cooperate to engage the intrinsic and extrinsic apoptotic cascades, and apoptosis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5658.
Controlled release of paclitaxel from photocrosslinked chitosan hydrogels and its subsequent effect on subcutaneous tumor growth in mice
Authors: Kiyohaya Obara, Masayuki Ishihara, Yuichi Ozeki, Takamitsu Ishizuka, Takuya Hayashi, Shingo Nakamura, Yoshio Saito, Hirofumi Yura, Takemi Matsui, Hidemi Hattori, Bonpei Takase, Miya Ishihara, Makoto Kikuchi, Tadaaki Maehara
Journal: Journal of Controlled Release (2005)
Anti-Semitism: A Disease of the Mind
Authors: Burton Einspruch
Journal: JAMA (1991)

Theodore Rubin, MD, a psychoanalyst, states in the preface to his fine work that he is "deeply concerned with the eradication of bigotry wherever it exists." To understand this phenomenon, he uses a disease concept with psychodynamic constructs. He proposes "symbol sickness" as the "major underlying and contributing psychological disablement making anti-Semitism and most other illnesses of this kind possible." Prominent aspects of symbol sickness include four primary characteristics: the symbol gap, ie, "the removal of the symbol from the object it initially is there to represent"; symbol autonomy, ie, "the symbol not only is removed from the subject but at least in part from the central thinking process of the host"; fragmentation, in which the emotionally laden symbol eventually eludes the control of the host's logical system and has the capacity to spread; and distortion, in which "the symbol is free to take on any and all grotesqueries however
Glucocorticoid receptor concentrations and terminal transferase activity as indicators of prognosis in acute non-lymphocytic leukaemia.
Authors: L Skoog, B Nordenskjold, A Ost, B Andersson, R Hast, N Giannoulis, S Humla, T Hagerstrom, P Reizenstein
Journal: BMJ (1981)

Activity of terminal deoxynucleotidyl transferase (TdT), adenosine deaminase, and 59nucleotidase and the cellular concentration of glucocorticoid (dexamethasone) receptor were determined in 25 patients with acute non-lymphocytic leukaemia. All patients were treated according to a common protocol. Increased activity of TdT (greater than 0.1 unit/microgram DNA) was found in 11 patients. This group of patients was shown to have higher remission and survival rates (p = 0.06) compared with patients with low activity of TdT. The glucocorticoid receptor concentration of the leukaemic blast cells ranged from 0 to 0.94 fmol/microgram DNA. Thirteen patients had blast cells with a glucocorticoid receptor concentration over 0.22 fmol/microgram DNA. These patients had significantly increased remission and survival rates (p = 0.006) compared with those with a low receptor concentration. This finding cannot be explained by a difference in sensitivity to glucocorticoids since these were not used as therapeutic agents. Adenosine deaminase and 59nucleotidase activities both varied within two orders of magnitude. No correlation could be found between activities of these enzymes and remission or survival rate. These results show that measurements of TdT activity and the glucocorticoid receptor concentration yield valuable prognostic information in acute non-lymphocytic leukaemia.
Association of Waist-Hip Ratio With Diabetes Mellitus: Strength and Possible Modifiers
Authors: Maria Inês Schmidt, Bruce B Duncan, Luis Henrique Canani, Cristina Karohl, Lloyd Chambless
Journal: Diabetes Care (1992)

To characterize the association between central obesity, as measured by the waist-hip ratio (WHR), and non-insulin-dependent diabetes mellitus (NIDDM), considering the effects of sex, age, overall obesity, and family history of diabetes.Case-control study nested within a community-based survey. We selected 151 subjects with NIDDM and 301 nondiabetic control subjects as a systematic sample of survey screening negative individuals.Odds ratios for NIDDM, comparing a high WHR (greater than or equal to 0.926 for men, greater than or equal to 0.83 for women) to a low WHR were 4.72 with a 95% confidence interval of 2.39-9.34, and 2.17 with a 95% confidence interval of 1.03-4.58, for women and men, respectively, controlling for age, overall obesity, and a family history of diabetes. Women with high WHRs in the presence of these risk factors are notably at risk for diabetes.Central obesity, as measured by the WHR, is importantly and independently associated with NIDDM.
EULAR recommendations for knee and hip osteoarthritis: a critique of the methodology
Authors: W Zhang, M Doherty
Journal: British Journal of Sports Medicine (2006)

The quality of the EULAR recommendations for the management of hip and knee osteoarthritis (OA) was evaluated using a validated instrument. The quality and methods were compared with other guidelines and recommendations. EULAR recommendations were found to be among the best for overall quality. They show strengths with respect to scope, rigour of development, and clarity, but weaknesses with respect to stakeholder involvement, applicability, and editorial independence. However, a principal strength is their attempt to fill the gap between guidelines based solely on either research evidence or expert opinion. The methods used to synthesise research evidence (systematic review) and expert opinion (Delphi exercise) are robust. Strength of recommendation, based on combined consideration of research evidence, clinical expertise, and perceived patient preference, is valid and approaches the true essence of “evidence based practice” that considers each of these different forms of evidence.
<i>Mental Disorders.</i>A Handbook for Students and Practitioners. By Hubert J. Norman, M. B., Ch. B. (Edin.), D. P. H. (Edin. and Glas.), Medical Superintendent, Camberwell House, London, Lecturer on Mental Disorders, Westminster Hospital Medical School. (<i>New York: William Wood &amp; Company, 51 Fifth Avenue. Edinburgh: E. &amp; S. Livingstone, 16 and 17 Teviot Place, MCMXXVIII.</i>)
Authors: None Dunton
Journal: American Journal of Psychiatry (1928)
Tissue-Resident Macrophages Self-Maintain Locally throughout Adult Life with Minimal Contribution from Circulating Monocytes
Authors: Daigo Hashimoto, Andrew Chow, Clara Noizat, Pearline Teo, Mary Beth Beasley, Marylene Leboeuf, Christian D. Becker, Peter See, Jeremy Price, Daniel Lucas, Melanie Greter, Arthur Mortha, Scott W. Boyer, E. Camilla Forsberg, Masato Tanaka, Nico van Rooijen, Adolfo García-Sastre, E. Richard Stanley, Florent Ginhoux, Paul S. Frenette, Miriam Merad
Journal: Immunity (2013)