tbuckley/cabot-search huggingface dataset:
LSD "Mainlining"
Authors: Barry J. Materson, Elizabeth Barrett-Connor
Journal: JAMA (1967)

THE usual oral dose (25μg to 150μg) of lysergic acid diethylamide (LSD) required for a desired psychedelic effect is far below that which causes other serious derangements directly attributable to its pharmacologic activity. Complications of the illicit oral use of the drug, despite larger doses, are also largely limited to its hallucinogenic and psychologic effect. Doses of 20μg/kg of body weight are known to have been taken without a lethal outcome.1To our knowledge no deaths directly related to the use of LSD have been reported, although it has been used unsuccessfully for suicide attempts. (The rare suicide associated with LSD use tends to occur days to months after administration of the drug to a disturbed person.2) Occasionally, a subject under the hallucinogenic influence of the drug will accomplish acts incompatible with life such as attempting unaided flight from the top of a multistory building.  The danger of
Suppression of B lymphopoiesis during normal pregnancy.
Authors: K L Medina, G Smithson, P W Kincade
Journal: The Journal of Experimental Medicine (1993)

We describe a dramatic reduction in numbers and activity of committed B lymphocyte precursors in the bone marrow of normal pregnant mice. Changes in cells responsive to IL-7 were evident as early as 6.5 d of pregnancy and values were < 10% of normal at parturition. B lineage precursors, identified by display of CD45R and absence of surface IgM, were also substantially depressed, and subpopulations representing different stages in the B lineage were assessed by three-color flow cytometry. Early pro-B cells are medium to large in size and have been previously characterized by low expression of the heat-stable antigen (HSA). This category of cells was not reduced, and in fact may have been slightly elevated, during pregnancy. In contrast, all subsequent populations of B lineage precursors, defined by patterns of expression of heat-stable and CD43 antigens, were substantially depressed. The immediate precursors of B cells (small pre-B cells) were identified by small size, expression of CD45R, absence of CD43, and lack of surface IgM. These were the most reduced of any phenotypically defined population in bone marrow. Numbers of newly formed B cells, characterized by the presence of sIgM, but not sIgD, were also diminished. However, B cells with a mature phenotype (sIgM+, sIgD+) were present in normal to somewhat elevated numbers. Mitogen-responsive B cells clonable in a semisolid agar assay were not significantly affected. A bromodeoxyuridine (BrdU) labeling technique was used to evaluate mitotic activity, which revealed an increased proportion of long-lived lymphocytes in the bone marrow of pregnant mice. These observations indicate that B lymphopoiesis is markedly downregulated during pregnancy and that all precursor populations beyond the early pro-B cell stage are affected. The pregnancy-related changes in bone marrow were selective for B lineage precursors, as cells expressing myeloid and erythroid markers were not reduced. In spleen, evidence was obtained for partial depletion of one subset of B cells. These cells, which have been reported to be recent immigrants from marrow, are characterized as having high levels of sIgM and HSA. Changes in other major B lymphocyte subsets in the spleen were less remarkable. When considered with results from the BrdU labeling procedure, the findings indicate that both production and export of lymphocytes from marrow may be substantially decreased. Numbers of B cell precursors were higher in postpartum animals whose litters were removed at birth, suggesting that lactation may prolong regeneration of lymphocyte production.(ABSTRACT TRUNCATED AT 400 WORDS)
THE NATURE OF SHOCK SYMPTOMS OCCASIONALLY FOLLOWING DRUGS OR VACCINES
Authors: E. F. MÜLLER
Journal: JAMA (1927)

The etiology and nature of certain manifestations following immediately or shortly after the injection of drugs or foreign proteins, such as serums, vaccines or nonspecific agents, have been the subject of studies since the first observations of these phenomena in medical therapy. The true recognition of their mechanism, i. e., the participation of the organs and tissues involved in such a general body reaction, had to be known in order to overcome the disturbances connected with them. <h3>PREVIOUS OBSERVATIONS</h3> It is quite easy to understand why the usual physiologic and pharmacologic methods have as yet failed to reveal the mechanism of these attacks, because of their appearance in human beings only and because of their apparent dependence on certain individual factors. Practitioners and clinicians know that certain patients will always react with an attack of more or less severity after the administration of serums or arsphenamines, while others tolerate high
Marijuana and Mutism
Authors: DAVID B. MARCOTTE
Journal: American Journal of Psychiatry (1972)

The development of an inability or an unwillingness to communicate verbally after inhaling marijuana is incidentally reported in the literature. The author cites four cases in which mutism is associated with the inhalation of hashish. There was evidence of organic brain syndrome in all patients. By inference, organic brain syndrome and mutism are thought to be dose-related effects of inhaling marijuana.
Disrupted Prenatal Maternal Cortisol, Maternal Obesity, and Childhood Wheeze. Insights into Prenatal Programming
Authors: Rosalind J. Wright, Kate Fisher, Yueh-Hsiu Mathilda Chiu, Robert O. Wright, Rebecca Fein, Sheldon Cohen, Brent A. Coull
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Exploring prenatal factors influencing childhood wheeze may inform programming mechanisms.Objectives: We examined associations among prenatal maternal cortisol profiles, maternal obesity, and repeated wheeze up to age 2 years (n = 261).Methods: Salivary cortisol was collected five times per day over 3 days at 29.0 ± 4.9 weeks gestation. Mothers were categorized as obese (body mass index ≥ 30 kg/m2) versus nonobese (body mass index < 30 kg/m2). Using logistic regression, we examined the influence of log-transformed cortisol metrics (level at each time point, morning rise, diurnal and afternoon slopes) and obesity on wheeze adjusting for covariates. Linear mixed models were implemented to examine associations between cortisol trajectories and wheezing. Interactions between maternal cortisol and obesity were considered.Measurements and Main Results: Mothers were primarily minority (56.5% Hispanic, 24.1% African American), 61% had less than or equal to 12 years of education, 34% were obese, and 8.4% of children had repeated wheeze. An interquartile range increase in mean log cortisol at bedtime (odds ratio, 2.2; 95% confidence interval, 1.09–4.09) and maternal obesity (odds ratio, 3.43; 95% confidence interval, 1.26–9.35) were independently associated with wheeze. Linear mixed models revealed an association between a flatter afternoon slope (slower decline in log cortisol per hour) and repeated wheeze in children of obese mothers (children with [−0.017 change] and without [−0.061 change] wheeze [P = 0.009 for time × wheeze interaction]), but not in children of nonobese mothers (with [−0.050 change] and without [−0.061 change] wheeze [P = 0.51]).Conclusions: Maternal prenatal cortisol disruption and obesity were independently associated with children's wheeze. Obese women with adverse cortisol profiles were most likely to have children with repeated wheeze.
Diabetic Lipemia
Authors: John D. Bagdade, Daniel Porte, Edwin L. Bierman
Journal: New England Journal of Medicine (1967)

DIABETIC lipemia (milky plasma), first described in the nineteenth century, remains a well recognized but rare manifestation of uncontrolled diabetes mellitus. Although prompt diagnosis and insulin treatment have probably reduced the incidence of hyperlipemia in symptomatic diabetes, reports of this poorly understood syndrome continue to appear.1 2 3>Since lipemia may be associated with varying degrees of carbohydrate intolerance in a wide spectrum of patients, the term "diabetic lipemia" will be restricted to describe the lipemia associated with severe symptomatic diabetes. This lipemia characteristically is abolished by insulin treatment. The patient with this clinical syndrome should be readily distinguished from the . . .
Urea and Protein Synthesis in Cold–Preserved Isolated Rat Hepatocytes
Authors: Paul K. Vreugdenhil, Diane C. Marsh, Folkert O. Belzer, James H. Southard
Journal: Hepatology (1992)

We used an isolated–hepatocyte model to study how hypothermic storage (simulating liver preservation) affects metabolism after prolonged preservation. Rat hepatocytes were stored in the University of Wisconsin solution for up to 72 hr. After each day of storage, protein synthesis, urea synthesis, ATP content and lactate dehydrogenase release were determined in rewarmed (37° C) and oxygenated hepatocytes. Protein synthesis ([ 3 H]–leucine incorporation into protein) was depressed by 16% ± 4%, 54% ± 6% and 69% 4% after 24 hr, 48 hr and 72 hr, respectively. Urea synthesis, ATP synthesis and lactate dehydrogenase release were similar to those in control hepatocytes (no preservation). Fasting of the rats before isolation of hepatocytes caused more rapid loss of protein–synthetis capabilities (59% in 24 hr) with no significant loss of lactate dehydrogenase, urea synthesis or ATP synthesis. Hepatocyte viability (lactate dehydrogenase release) as judged by membrane permeability, ATP synthesis and potassium content can be maintained after up to 6 days of cold storage. However, protein synthesis is depressed after only 48 hr of cold storage. Thus hypothermic storage of the liver causes a change in the metabolic capabilities of the hepatocytes, and the timing of the loss of protein synthesis is similar to the limits of successful cold storage of the whole liver (48 hr). Thus a limit to long–term storage of the liver may be related to loss of protein synthesis. In liver transplantation, one indication of poor preservation is a decrease in serum albumin and clotting factors with increased tissue edema and bleeding diathesis. Livers from fasted animals (or donors) may be more sensitive to preservation injury because of the more rapid loss of protein synthesis. The mechanism for loss of proteinsynthesis capabilities is not related to a decrease in ATP but may be due to changes in cellular content of RNA or DNA. Preservation of the loss of the capability of the hepatocytes to synthesize protein may be a key to obtaining excellent–quality long–term liver preservation. (Hepatology 1992;16:241-246.)
At last: Serious consideration
Authors: David L. Hull, Rodney E. Langman, Sigrid S. Glenn
Journal: Behavioral and Brain Sciences (2001)

For a long time, several natural phenomena have been considered unproblematically selection processes in the same sense of “selection.” In our target article we dealt with three of these phenomena: gene-based selection in biological evolution, the reaction of the immune system to antigens, and operant learning. We characterize selection in terms of three processes (variation, replication, and environmental interaction) resulting in the evolution of lineages via differential replication. Our commentators were largely supportive with respect to variation and environmental interaction but critical with respect to replication, in particular its appeal to information. With some reservations, our commentators think that our general analysis of selection may fit gene-based selection in biological evolution and the reaction of the immune system but not operant learning. If nothing else, this article shows that the notion of selection is not as straightforward as it may seem.
Severe postherpetic neuralgia and other neuropathic pain syndromes alleviated by topical gabapentin
Authors: S. Hiom, G.K. Patel, R.G. Newcombe, S. Khot, C. Martin
Journal: British Journal of Dermatology (2014)

Journal Article Severe postherpetic neuralgia and other neuropathic pain syndromes alleviated by topical gabapentin Get access S. Hiom, S. Hiom Research and Development St. Marys Pharmaceutical Unit Cardiff and Vale University Health Board Cardiff U.K Search for other works by this author on: Oxford Academic Google Scholar G.K. Patel, G.K. Patel Department of Dermatology Prince Philip Hospital Hywel Dda University Health Board Carmarthenshire U.K Search for other works by this author on: Oxford Academic Google Scholar R.G. Newcombe, R.G. Newcombe Cochrane Institute of Primary Care and Public Health School of Medicine Cardiff University Cardiff U.K Search for other works by this author on: Oxford Academic Google Scholar S. Khot, S. Khot Complex Pain Clinic Department of Anaesthesia, Intensive Care and Pain Medicine; Cardiff and Vale University Health Board Cardiff U.K Search for other works by this author on: Oxford Academic Google Scholar C. Martin C. Martin Research Associate, St Mary's Pharmaceutical Unit Cardiff and Vale University Health Board Cardiff U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 1, 1 July 2015, Pages 300–302, https://doi.org/10.1111/bjd.13624 Published: 01 July 2015
Aire Controls Mesenchymal Stem Cell-mediated Suppression in Chronic Colitis
Authors: Biju Parekkadan, Anne L Fletcher, Matthew Li, Melissa Y Tjota, Angelique Bellemare-Pelletier, Jack M Milwid, Je-Wook Lee, Martin L Yarmush, Shannon J Turley
Journal: Molecular Therapy (2011)

Mesenchymal stem cells (MSCs) are emerging as a promising immunotherapeutic, based largely on their overt suppression of T lymphocytes under inflammatory and autoimmune conditions. While paracrine cross-talk between MSCs and T cells has been well-studied, an intrinsic transcriptional switch that programs MSCs for immunomodulation has remained undefined. Here we show that bone marrow-derived MSCs require the transcriptional regulator Aire to suppress T cell-mediated pathogenesis in a mouse model of chronic colitis. Surprisingly, Aire did not control MSC suppression of T cell proliferation in vitro. Instead, Aire reduced T cell mitochondrial reductase by negatively regulating a proinflammatory cytokine, early T cell activation factor (Eta)-1. Neutralization of Eta-1 enabled Aire(-/-) MSCs to ameliorate colitis, reducing the number of infiltrating effector T cells in the colon, and normalizing T cell reductase levels. We propose that Aire represents an early molecular switch imposing a suppressive MSC phenotype via regulation of Eta-1. Monitoring Aire expression in MSCs may thus be a critical parameter for clinical use.
The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4α
Authors: Laura Santangelo, Alessandra Marchetti, Carla Cicchini, Alice Conigliaro, Beatrice Conti, Carmine Mancone, Jessica A. Bonzo, Frank J. Gonzalez, Tonino Alonzi, Laura Amicone, Marco Tripodi
Journal: Hepatology (2011)

The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase chain reaction. HNF4α recruitment on promoters of both mesenchymal and EMT regulator genes was determined by way of electrophoretic mobility shift assay and chromatin immunoprecipitation. The effect of HNF4α depletion was assessed in silenced cells and in the context of the whole liver of HNF4 knockout animals. Our results identified key EMT regulators and mesenchymal genes as new targets of HNF4α. HNF4α, in cooperation with its target HNF1α, directly inhibits transcription of the EMT master regulatory genes Snail, Slug, and HMGA2 and of several mesenchymal markers. HNF4α-mediated repression of EMT genes induces MET in hepatomas, and its silencing triggers the mesenchymal program in differentiated hepatocytes both in cell culture and in the whole liver. Conclusion: The pivotal role of HNF4α in the induction and maintenance of hepatocyte differentiation should also be ascribed to its capacity to continuously repress the mesenchymal program; thus, both HNF4α activator and repressor functions are necessary for the identity of hepatocytes. (HEPATOLOGY 2011;)
ET-39 * REPEATED PHARMACOLOGICAL DOSES OF ASCORBATE PROTECTS TUMOURS FROM RADIATION DAMAGE IN AN INTRACRANIAL MOUSE GLIOMA MODEL
Authors: M. McConnell, C. Grasso, M.-S. Fabre, S. Collis, L. Castro, N. Schleich, P. Herst
Journal: Neuro-Oncology (2014)

High dose ascorbate is used as an anti-cancer treatment by complementary and alternative medicine. In the acidic, metal-rich tumour environment ascorbate acts as a pro-oxidant, generating free radicals and DNA damage, similar to ionising radiation. We showed that addition of high-dose ascorbate to radiation blocked repair of radiation-induced DNA damage in primary GBM cell lines, effectively radio-sensitising. We examined the effect of ascorbate and radiation on the murine glioma GL261 in vitro, and combined with intra-peritoneal ascorbate in an intra-cranial GL261 model. As previously seen, high dose ascorbate radio-sensitized GL261 cells in a clonogenicity assay. Tumour-bearing mice were treated with: 4.5Gy to the brain 8 days post-implantation; repeated high-dose ascorbate from day 8-45; both treatments; or no treatment. While radiation increased survival, intraperitoneal ascorbate alone had no effect. In contrast with in vitro data, tumour-bearing mice treated with radiation and daily ascorbate had poorer survival than those treated with radiation alone. Histological analysis of the tumours showed less necrosis and bleeding within tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. While the mechanism of protection is not yet defined, this finding might have important clinical implications for combining high-dose ascorbate with radiation therapy.
U.S. Funding Is Insufficient to Address the Human Health Impacts of and Public Health Responses to Climate Variability and Change
Authors: Kristie L. Ebi, John Balbus, Patrick L. Kinney, Erin Lipp, David Mills, Marie S. O’Neill, Mark L. Wilson
Journal: Environmental Health Perspectives (2009)

The need to identify and try to prevent adverse health impacts of climate change has risen to the forefront of climate change policy debates and become a top priority of the public health community. Given the observed and projected changes in climate and weather patterns, their current and anticipated health impacts, and the significant degree of regulatory discussion underway in the U.S. government, it is reasonable to determine the extent of federal investment in research to understand, avoid, prepare for, and respond to the human health impacts of climate change in the United States.In this commentary we summarize the health risks of climate change in the United States and examine the extent of federal funding devoted to understanding, avoiding, preparing for, and responding to the human health risks of climate change.Future climate change is projected to exacerbate various current health problems, including heat-related mortality, diarrheal diseases, and diseases associated with exposure to ozone and aeroallergens. Demographic trends and geophysical and socioeconomic factors could increase overall vulnerability. Despite these risks, extramural federal funding of climate change and health research is estimated to be < $3 million per year.Given the real risks that climate change poses for U.S. populations, the National Institutes of Health, Centers for Disease Control and Prevention, U.S. Environmental Protection Agency, and other agencies need to have robust intramural and extramural programs, with funding of > $200 million annually. Oversight of the size and priorities of these programs could be provided by a standing committee within the National Academy of Sciences.
Asp f6, an Aspergillus allergen specifically recognized by IgE from patients with allergic bronchopulmonary aspergillosis, is differentially expressed during germination
Authors: M. Schwienbacher, L. Israel, J. Heesemann, F. Ebel
Journal: Allergy (2005)

Background: Aspergillus fumigatus is a pathogenic mould causing allergic and invasive respiratory diseases. Allergic bronchopulmonary Aspergillosis (ABPA) is a severe pulmonary complication resulting from hypersensitivity to A. fumigatus proteins. Aspergillus allergen Asp f6 is recognized by IgE from ABPA patients, but not from sensitized individuals, a fact that can be used to differentiate between these two groups of allergic patients. Methods: Proteins from hyphae, resting and germinating conidia of A. fumigatus were compared by SDS‐PAGE. Protein identification was performed using MALDI‐TOF mass spectrometry. Recombinant A. fumigatus allergens were used to isolate specific monoclonal antibodies (mab) from a hybridoma bank generated against Aspergillus proteins. Results: A hyphae‐specific 23 kDa A. fumigatus protein was identified as the allergen Asp f6/manganese‐dependent superoxide dismutase (MnSOD). Differential expression of MnSOD was confirmed by immunoblot using a specific mab. In contrast, Asp f8 another intracellular, but not ABPA‐specific allergen, was detected in hyphae and conidia. Conclusions: Aspergillus fumigatus is able to colonize its environment by the formation of hyphae. Hyphae are found in the lung of ABPA patients, but not in patients suffering from atopic asthma. Our finding that Asp f6 is specifically expressed in hyphae might explain why an IgE response to Asp f6 is specific for ABPA patients.
Dutch medical alliance moves to change thinking on male circumcision
Authors: T. Sheldon
Journal: BMJ (2010)

A broad alliance of medical organisations in the Netherlands has officially adopted the view that circumcision of underage boys without a medical reason violates children’s human rights and contravenes the Dutch constitution.

The Dutch Medical Association has spearheaded the move, arguing that the medical benefits of circumcision are unproved whereas complications are underestimated, and urging “a strong policy of deterrence.” Doctors should “actively and insistently” inform parents seeking to have their child circumcised about the association’s stance.

It is estimated that up to15 000 circumcisions of boys under 16 are carried out each year in the Netherlands—largely for religious or cultural reasons—among Jewish, Muslim, and African Christian communities.

The association thinks …