tbuckley/cabot-search huggingface dataset:
Recovery of Adrenal Function after Substitution of Beclomethasone Dipropionate for Oral Corticosteroids
Authors: D. J. Maberly, G. J. Gibson, A. G. Butler
Journal: BMJ (1973)

<h3>Summary</h3> Late-onset Alzheimer’s Disease (LOAD) pathology is rare in our closest living evolutionary relatives (chimpanzees), which also express much lower microglial levels of CD33(Siglec-3)–a myelomonocytic receptor inhibiting innate immune reactivity by extracellular V-set domain recognition of sialic acid(Sia)-containing “self-associated molecular patterns” (SAMPs). We earlier showed that V-set domain-deficient <i>CD33</i>-variant allele, protective against LOAD, is derived and specific to hominin-lineage. We now report that <i>CD33</i> also harbors multiple hominin-specific V-set domain mutations and explore selection forces that may have favored such genomic changes. <i>N</i>-glycolylneuraminic acid (Neu5Gc), the preferred Sia-ligand of ancestral CD33 is absent in humans, due to hominin-specific, fixed loss-of-function mutation in CMAH, which generates CMP-Neu5Gc from its precursor, CMP-<i>N</i>-acetylneuraminic acid (Neu5Ac). Extensive mutational analysis and MD-simulations indicate that fixed change in amino acid 21 of hominin V-set domain and conformational changes related to His45 corrected for Neu5Gc-loss by switching to Neu5Ac-recognition. Considering immune-evasive “molecular mimicry” of SAMPs by pathogens, we found that human-specific pathogens <i>Neisseria gonorrhoeae</i> and Group B <i>Streptococcus</i> (affecting fertility and fetuses/neonates respectively) selectively bind huCD33 and this binding is significantly impacted by amino acid 21 modification. Alongside LOAD-protective <i>CD33</i> alleles, humans harbor additional, derived, population-universal, cognition-protective variants absent in “great ape” genomes. Interestingly, 11 of 13 SNPs in these human genes (including <i>CD33</i>), that protect the cognitive health of elderly populations, are not shared by genomes of archaic hominins: Neanderthals and Denisovans. Finally, we present a plausible evolutionary scenario to compile, correlate and comprehend existing knowledge about huCD33 evolution and suggest that grandmothering emerged in humans.
BOTULISM. STUDIES ON THE MANNER IN WHICH THE TOXIN OF CLOSTRIDIUM BOTULINUM ACTS UPON THE BODY
Authors: Ernest C. Dickson, Richard Shevky
Journal: The Journal of Experimental Medicine (1923)

A survey of the results of these experiments shows, we believe conclusively, that in botulinus intoxication in cats, dogs, and rabbits there is a specific effect upon the portions of the autonomic nervous system which Gaskell (14) described as the bulbosacral and prosomatic outflows of connector fibers respectively, which results in a blocking of the nerve impulses of these nerves. The experimental as well as the clinical evidence indicates that there is no damage to the nerves of the thoracicolumbar outflow. The exact location of the damage has not been ascertained nor has the mechanism by which the nerve impulse is blocked been determined. The experiments show, however, that the lesions in these portions of the nervous system are not of central distribution but are peripheral, and that the block cannot be due to an organic break in the conduction apparatus but must be due to some derangement which is relatively unstable. If it were otherwise it would not be possible to induce a physiological response even by massive stimulation, nor could the response be subsequently repeated by stimuli which lie within the limits of normal intensity. The application of the results of these experiments to the clinical manifestations of botulism will be discussed in a later report after the effect of the toxin upon the skeletal motor nerves has been described.
Energetics of sodium transport in the urinary bladder of the toad. Effect of aldosterone and sodium cyanide.
Authors: N Cortas, E Abras, M Arnaout, A Mooradian, S Muakasah
Journal: Journal of Clinical Investigation (1984)

Experiments were designed to determine whether the stimulatory effect of aldosterone on sodium transport involves an increase in tissue ATP. Urinary bladders that were removed from toads presoaked in 0.6% saline for 48-72 h, mounted as sacs, and maintained in open circuit except for brief observation of short circuit current every 30 min responded to 100 nM aldosterone added to the serosal bath with an increase in short circuit current to 170% of control hemibladders, which plateaus at 2-3 h. Tissue (ATP)/(ADP) X (Pi) measured in perchloric acid extracts increased to a maximum of 208% of controls (P less than 0.001) and ATP increased to 116% of controls (P less than 0.01) at 180 min. The short circuit current response to aldosterone paralleled the increase in ATP and (ATP)/(ADP) X (Pi) measured at 75, 120, 180, and 240 min. In bladders clamped at -150 mV, the short circuit current response to aldosterone was greater: 280% of controls (P less than 0.001) and tissue (ATP)/(ADP) X (Pi) increased to 191% of controls (P less than 0.001). In continuously short circuited bladders and bladders clamped at +75 mV, the short circuit current response to aldosterone and the change in ATP, ADP, or Pi were markedly diminished. 100 microM amiloride added to mucosal bath decreased the short circuit current to zero and inhibited the short circuit current response to aldosterone, whereas tissue ATP increased to 141% (P less than 0.05). 100, 250, and 500 microM NaCN dropped the short circuit current to 59, 35, and 24% of control values, respectively. Concurrently, tissue ATP measured at 60 min after the addition of NaCN dropped to 79, 66, and 56% of control values, respectively, and tissue ATP/ADP dropped to 68, 50, and 40%, respectively. The data revealed significant correlation between the change in the rate of sodium transport produced by aldosterone or NaCN as measured by the short circuit current and the concentration of ATP (r = 0.96, P less than 0.001), as well as ATP/ADP (r = 0.95, P less than 0.001). In conclusion, these results support the view that the stimulatory effects of aldosterone on sodium transport involve an increase in ATP or (ATP)/(ADP) X (Pi).
Psychosomatic Medicine: a Meeting Ground for Oriental and Occidental Medical Theory and Practice
Authors: Morton F. Reiser
Journal: Psychotherapy and Psychosomatics (1979)

This paper makes three major points indicating that the field of psychosomatic medicine represents a common meeting ground for Eastern-Western medical theory and practice. The first point emphasizes that oriental physicians raised in Eastern religious and philosophical environment can more readily accept the importance of spiritual experience in their practice of medicine as well as in the conduct of family life and social relationships. Oriental theories of medicine and treatment have for some time reflected, accommodated, and incorporated principles, techniques, and practices from Zen, Yoga, various forms of meditation, etc. On the other hand, Western physicians have been grounded in a more mechanistic philosophical matrix and developed more and more sophistication in biology and increasingly reductionistic biomedical models of disease. While they remained mindful of the clinical correlations between psychosocial stress and vicissitudes of illness, they preferred to a large degree to relegate this aspect to the 'art of medicine' and with some notable exceptions left the field largely to the psychiatric, psychologic and social disciplines. The second point is that the past two decades, however, have seen tremendous advances in neurobiological sciences which powerfully implicate central nervous system mechanisms – particularly psychoneuroendocrine reactions to stress, including psychosocial stress, in pathogenesis of medical illness. These developments virtually demand a bio-psychosocial model and are forcing the attention of physicians – both internists and psychiatrists – in the United States (and many other parts of the West) back to confronting mysteries of mind-brain and brain-body relationships. These developments point increasingly as well to the importance and great potential of psychoanalysis both as theory and method for participating in and contributing to further progress in psychosomatic medicine. The major thrust of these advances has made it clear that states of health and illness can only be understood fully in terms of three parameters, the biological, psychological, and social. The third point is that the complex of central nervous system mechanisms that link the psychosocial realm with the physiologic realm are vitally involved in maintenance of health. For a variety of empirical and theoretical reasons, relaxation and biofeedback methods as well as various forms of psychotherapy and sociotherapy are now finding their way into medical practice and research in the United States along with more conventional and long accepted procedures and practices. The East-West gap or polarity is fast disappearing.
The Federal Involvement in Health
Authors: Charles C. Edwards
Journal: New England Journal of Medicine (1975)

THE remarkable expansion of federal activity in the health field in recent years, an expansion measured not simply in increased levels of spending, but perhaps more pointedly in the trend toward greater federal involvement in issues such as the quality and cost of care, the deployment of physicians and other health personnel, the selection of biomedical research priorities and methods, and the capacity of the health-care system to respond effectively to the demands that could soon be imposed on it by national health insurance, has produced a spectrum of reactions ranging, I suspect, from despair to euphoria. I think it . . .
A Src/Abl Kinase Inhibitor, SKI-606, Blocks Breast Cancer Invasion, Growth, and Metastasis <i>In vitro</i> and <i>In vivo</i>
Authors: Houda Jallal, Maria-Luisa Valentino, Gaoping Chen, Frank Boschelli, Suhad Ali, Shafaat A. Rabbani
Journal: Cancer Research (2007)

The central role of Src in the development of several malignancies, including breast cancer, and the accumulating evidence of its interaction with receptor tyrosine kinases, integrins, and steroid receptors have identified it as an attractive therapeutic target. In the current study, we have evaluated the effect of a Src/Abl kinase inhibitor, SKI-606, on breast cancer growth, migration, invasion, and metastasis. Treatment of human breast cancer cells MDA-MB-231 with SKI-606 caused a marked inhibition of cell proliferation, invasion, and migration by inhibiting mitogen-activated protein kinase and Akt phosphorylation. For in vivo studies, MDA-MB-231 cells transfected with the plasmid encoding green fluorescent protein (GFP; MDA-MB-231-GFP) were inoculated into the mammary fat pads of female BALB/c nu/nu mice. Once tumor volume reached 30 to 50 mm(3), animals were randomized and treated with vehicle alone or 150 mg/kg SKI-606 by daily oral gavage. Experimental animals receiving SKI-606 developed tumors of significantly smaller volume (45-54%) compared with control animals receiving vehicle alone. Analysis of lungs, liver, and spleen of these animals showed a significant decrease in GFP-positive tumor metastasis in animals receiving SKI-606 at a dose that was well tolerated. Western blot analysis and immunohistochemical analysis of primary tumors showed that these effects were due to the ability of SKI-606 to block tumor cell proliferation, angiogenesis, growth factor expression, and inhibition of Src-mediated signaling pathways in vivo. Together, the results from these studies provide compelling evidence for the role of Src inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.
Hepatocellular carcinoma complicating autoimmune hepatitis: Role of hepatitis C virus
Authors: Stephen D. Ryder, John Koskinas, Paolo M. Rizzi, Ian G. McFarlane, Bernard C. Portmann, Nikolai V. Naoumov, Roger Williams
Journal: Hepatology (1995)

The risk of hepatocellular carcinoma in autoimmune hepatitis is low, even in patients with long-standing cirrhosis. Because of the increasing recognition of an association of hepatitis C virus (HCV) with autoimmune hepatitis, at least in some geographical areas, and with hepatocellular carcinoma (HCC) (hepatoma), we have examined eight cases (4 male, 4 female) who presented between 1985 and 1993 with hepatoma complicating autoimmune hepatitis. All had steroid-responsive autoimmune hepatitis with serum anti-smooth muscle and antinuclear autoantibodies. Median duration of disease was 17.1 years, and all patients had biopsy-proven cirrhosis. One patient had a history of intravenous drug abuse, and four had previously received blood transfusions. Serum samples (stored at −20°C from up to 9 years before diagnosis of hepatoma) were tested for anti-hepatitis C virus antibodies by a second-third-generation assay and for HCV RNA by the polymerase chain reaction method using primers from the 5′noncoding region. Tissue from liver adjacent to tumor areas was subjected to polymerase chain reaction along with tissue from previous liver biopsy specimens (taken up to 19 years before diagnosis of hepatoma) in all patients. Six patients had evidence of HCV infection: four seropositive for HCV RNA (two of whom were also anti-HCV positive) and two seronegative for HCV RNA and anti-HCV but with HCV RNA in liver tissue at presentation with hepatoma. Retrospective testing showed probable acquisition of HCV through blood transfusion in the four transfused patients. The findings suggest that HCV may have oncogenic potential and that hepatoma complicating autoimmune hepatitis is associated with unsuspected HCV infection in most cases in our series. Screening of liver for HCV RNA should be considered in autoimmune hepatitis patients with a previous history of parenteral exposure to blood, and for hepatoma in those found to have HCV infection. (Hepatology 1995; 22:718–722.)
Abstract 2964: YB-1 expression in early hematopoiesis and leukemic cells
Authors: Jasjeet Bhullar, Vincent E. Sollars
Journal: Cancer Research (2010)

Abstract Hematopoietic transcription factors play a critical role in directing the commitment and differentiation of hematopoietic stem cells (HSC) along a particular lineage. Y box protein (YB-1), a cold shock family protein is a transcription factor which is widely expressed throughout development and has been implicated as a cell survival factor that regulates transcription and translation. YB-1 is known to be involved in erythroid cell development by interacting with Globin Transcription Factor (GATA); this study aims to investigate YB-1 expression in normal hematopoietic differentiation and leukemia. EML-clone 1 cells, a murine hematopoietic stem cell line, was used as a model for looking at the expression of YB-1 during myeloid differentiation by western blotting and quantitative RT-PCR. Fluorescence activated cell sorting was conducted to isolate lineage——/IL-7R—/c-kit+/Sca1+ (LKS) hematopoietic stem, lineage——/IL-7R—/c-kit+/Sca1— myeloid progenitor cells and granulocytes from mouse bone marrow to assess the YB-1 expression in vivo. YB-1 protein levels were analyzed in a panel of myeloid leukemic cell lines by immunoblotting. YB-1 mRNA and protein levels were high in the EML cells but the expression goes down in RA/IL-3 treated EML-clone 1 cells (myeloid progenitors) and was even more dramatically down-regulated in GM-CSF treated EML cells during the course of myeloid differentiation. Interestingly, LKS (enriched fraction of hematopoietic stem cells) and myeloid progenitor cells showed high level of YB-1 expression as compared to the differentiated cells like granulocytes. Further, we observed that YB-1 protein was expressed in several myeloid leukemic cell lines blocked at different stages of myeloid development. Thus, our data suggest that YB-1 is down-regulated during myeloid differentiation and it might be involved in hematopoietic differentiation. Aberrant YB-1 expression could be a contributing factor in the development of leukemia thus making it an excellent molecular target for therapy in myeloproliferative disorders and leukemia. 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 2964.
Treatment of Hydrazine-Induced Coma with Pyridoxine
Authors: James K. Kirklin, Marc Watson, Conrado C. Bondoc, John F. Burke
Journal: New England Journal of Medicine (1976)

Hydrazine (H2N-NH2), a volatile chemical deoxygenator, is widely used in industry as a corrosion inhibitor and in the military as a rocket propellant.1 In laboratory animals it produces convulsions, circulatory collapse, pulmonary edema, hypoglycemia, emesis, interstitial nephritis, and hepatocellular damage.2 , 3 Chronic exposure in human beings can cause pneumonia, hepatocellular damage, nephritis and acute tubular necrosis.1 Acute toxicity may in addition result in seizures or coma.4 Pyridoxine is an effective antidote against hydrazine-induced seizures in rats,5 but has rarely been reported as an antidote for human hydrazine poisoning.6 Case ReportA 36-year-old man was transferred to the . . .
Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid
Authors: Hidesaku Asakura, Yoko Sano, Tomotaka Yoshida, Mika Omote, Yasuo Ontachi, Tomoe Mizutani, Masahide Yamazaki, Eriko Morishita, Akiyoshi Takami, Ken-ichi Miyamoto, Shinji Nakao
Journal: Intensive Care Medicine (2004)
Lichen-planus-like eruption: a marker for chronic graft-versus-host reaction.
Authors: J H Saurat, E Gluckman
Journal: BMJ (1977)

continuing and expanding research on the treatment of this condition, which is at present responsible for considerable personal distress and social disruption.In view of the large numbers of women between the menarche and the menopause who suffer from PMS any significant reduction in its overall incidence will be welcome and we hope that family doctors will be encouraged to treat PMS by these new approaches.Further help and support from specialised clinics in teaching hospitals and other centres will be required for some time yet, but we hope soon to publish further observations on the clinical presenta- tion of PMS which will minimise this need.
Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival
Authors: Farshid Dayyani, Jianfeng Wang, Jing-Ruey J. Yeh, Eun-Young Ahn, Erica Tobey, Dong-Er Zhang, Irwin D. Bernstein, Randall T. Peterson, David A. Sweetser
Journal: Blood (2008)
Microvascular pressures and resistances in the left ventricular subepicardium and subendocardium.
Authors: W M Chilian
Journal: Circulation Research (1991)

These experiments tested the hypothesis that differences in the distribution of subepicardial and subendocardial microvascular resistances may alter the transmural distributions of microvascular pressures. Isolated blood- and physiological saline-perfused porcine hearts were surgically incised to enable exposure of the subendocardial and subepicardial microcirculations. Microvascular pressures were measured during cardiac arrest and maximal vasodilation at various perfusion pressures to formulate relations between perfusion pressure and microvascular pressure in the different subendocardial (both free wall and papillary muscle) and subepicardial segments. Measurements of arteriolar and venular pressures in both myocardial regions were performed in comparably sized vessels (80-120 microns in diameter). At a coronary perfusion pressure of 100 mm Hg, subendocardial arteriolar and venular pressures were 60 +/- 4 and 33 +/- 3 mm Hg, respectively. In contrast, at the same coronary perfusion pressure, arteriolar and venular pressures in the subepicardial microcirculation averaged 80 +/- 6 and 22 +/- 3 mm Hg, respectively (p less than 0.05 versus subendocardium). At all levels of coronary perfusion pressure, arteriolar pressures were significantly lower in the subendocardium than in the subepicardium (p less than 0.05). Venular pressures were also higher in the subendocardial microcirculation than in the subepicardial microcirculation at all but the lowest perfusion pressure (p less than 0.05). The relative distribution of resistances in arteries, microvessels, and veins was also different between the subepicardium and subendocardium. Specifically, in the subendocardium, arterial and venous resistances were higher, percentage-wise, but microvascular resistance was proportionately lower than that in the subepicardium (p less than 0.05). From these data, it is concluded that the distribution of microvascular resistances and pressures is different during maximal vasodilation in the subepicardial and subendocardial microcirculations of the left ventricle. It is also speculated that differences in autoregulatory capacity and vulnerability to ischemia may be partially related to unequal distribution of microvascular resistances across the wall of the left ventricle.
Signal transduction systems and atrial fibrillation
Authors: A Goette
Journal: Cardiovascular Research (2002)

Cell communication, an essential component of integrated physiological function in multicellular organisms, is mediated largely through informational molecules, such as hormones and neurotransmitters. After binding to specific receptors, these first messengers activate intracellular signaling cascades and, thereby, translate extracellular messenger levels into intracellular events. Atrial fibrillation is associated with significant electrophysiological and structural alterations of atrial tissue. Most of these changes seem to be related to activation of signal transduction systems at the molecular atrial level. This review will describe the role and regulation of different signal transduction systems in fibrillating atria.
Discontinuation of Antistreptococcal Prophylaxis
Authors: Alvan R. Feinstein
Journal: JAMA (1966)

Antistreptococcal prophylaxis was discontinued, by double-blind techniques, in selected older adolescents, without heart disease, who had remained free of recurrent rheumatic fever for 3 to 5 years after an unequivocal episode. In 138 patient-years of observation, the group receiving oral potassium penicillin G, 200,000 units daily, developed 30 streptococcal infections (attack rate, 22%) and 1 rheumatic recurrence (attack rate, 0.7%). During 140 patient-years, the placebo group developed 30 streptococcal infections (attack rate, 21%) and 2 rheumatic recurrences (attack rate, 1.4%). None of the attack rate differences was statistically significant, and no overt new cardiac damage appeared in the three patients who developed rheumatic recurrences. Further studies would be desirable to determine the value of maintaining (or discontinuing) prophylaxis in the particular type of patient described here.
Twenty five years on
Authors: D Sloan
Journal: BMJ (1994)

I will never forget the 14 and 15 August 1969 and neither will my father, then a general practitioner in troubled west Belfast. The civil disturbances as they were officially called had been building up over the months throughout the province. Now the major rioting in Londonderry had raised the tension in the cockpit city of Belfast to boiling point.

My father's practice was half Protestant and half Catholic, and journeying between the Protestant Shankill Road and the Catholic Falls Road it was obvious that an explosion was imminent. No one, however, was fully prepared for the violence of that explosion. Over the night of 14 August there were fierce riots and gun battles, a dozen or so dead, hundreds injured, and homes and factories left blazing.

I came down the stairs to breakfast to find distraught parents in the hall. My father had just …