tbuckley/cabot-search huggingface dataset:
Tyramine kinetics and metabolism in cirrhosis.
Authors: B A Faraj, J T Fulenwider, E B Rypins, B Nordlinger, G L Ivey, R D Jansen, F M Ali, V M Camp, M Kutner, F Schmidt, D Rudman
Journal: Journal of Clinical Investigation (1979)

Hypertyraminemia is common in hepatic cirrhosis and correlates in severity with encephalopathy. The mechanism of cirrhotic hypertyraminemia has not been established. The alternative possibilities are increased production from tyrosine and impaired degradation by monoamine oxidase. This investigation determined the pharmacokinetics of tyramine after an intravenous bolus injections of [3H]-tyramine (180--200 muCi 12 Ci/mmol sp act) in 13 cirrhotics and 9 controls. In normals, [3H]tyramine levels initially declined rapidly (alpha-phase) followed by a slower decline (beta-phase) with an average t 1/2 of 20.8 min. Average normal metabolic clearance rate and production rate were 13.2 liters/min and 15.4 microgram/min, respectively. In cirrhotic patients, the plasma disappearance curve for [3H]tyramine was qualitatively similar to that of the control subjects with no apparent different in beta-t 1/2 (17.2 min). The hypertyraminemia of cirrhosis resulted primarily from overproduction of tyramine, as the production rate (32.0 microgram/min) in these patients was significantly greater (P less than 0.05) than in controls, whereas the metabolic clearance rate remained normal (average 12.2 liters/min). A difference in ratio of tyramine metabolic products was noted as well. Cirrhotics had a high ratio of plasma 4-hydroxyphenylethanol:4-hydroxyphenylacetic acid (60:40 vs. 30:70) as compared with normals. Although the tyramine clearance rates are similar in normals and cirrhotics, different mechanisms may be responsible for catabolism.
Abstract 906: Healing of Thin-Capped Fibroatheroma Assessed by Serial VH-IVUS Tissue Characterization
Authors: Takashi Kubo, Akiko Maehara, Gary S Mintz, Hiroshi Doi, Kenichi Tsujita, Junqing Yang, Jian Liu, Carlos Oviedo, Anthony Tam, Harpreet Bharaj, Richard Abendroth, Sinan Biro, Rasha Aaskar, Celia Castellanos, Lokesh Dani, Jeffrey W Moses, Geoffrey Vince, Pauliina Margolis, James R Margolis, Gregg W Stone, Martin B Leon
Journal: Circulation (2008)

Thin-cap fibroatheromas (TCFA) are prone to plaque rupture and thrombosis. Intravascular ultrasound (IVUS) virtual histology (VH) assesses plaque composition and lesion morphology in vivo. Methods &amp; Results: We used serial (baseline and follow-up @11 mos) VH-IVUS to study non-culprit plaque morphology in 221 lesions (plaque burden &gt;40%) in 106 pts. Lesions were classified into 4 types based on plaque composition; pathological intimal thickening (PIT), thin-capped fibroatheroma (TCFA), thick-capped fibroatheroma (ThCFA), fibrotic/fibrocalcific. At baseline, 21 lesions were TCFAs (confluent necrotic core contacting to the lumen). Overall during follow-up (Figure ), 16/21 (76%) TCFAs healed: 13 became ThCFAs, 2 TCFAs became PIT, 1 TCFA became fibrotic, and 5 TCFAs (24%) remains unchanged although the location of the necrotic core in contact with the lumen shifted axially. Compared to TCFAs that healed, TCFAs that remained TCFAs were more often proximal in location (distance from coronary ostium to the lesion of 19±6 vs. 41±22mm, respectively, p=0.037) and had larger lumen area (9.9±3.1 vs. 6.9±1.8 mm2, p=0.013), vessel area (22.8±6.4 vs. 15.3±2.6 mm2, p=0.001), plaque area (12.9±4.9 vs. 8.4±1.7 mm2, p=0.005), calcium area (1.3±0.6 vs. 0.6±0.3 mm2, p=0.014), and necrotic core area (2.6±1.0 vs. 1.6±0.7 mm2, p=0.015). In addition, 6 new TCFAs developed; these 6 late-developing TCFAs had the appearance of PIT at baseline (Figure ). Conclusion: Although most TCFAs seem to stabilize or heal during 12 mos follow-up, proximal TCFAs in larger vessels with more plaque and calcium and a larger necrotic core appear to heal less often and new TCFAs can develop.
T cell receptor variable gene usage in a specific cytotoxic T cell response. Primary structure of the antigen-MHC receptor of four hapten-specific cytotoxic T cell clones.
Authors: A Iwamoto, P S Ohashi, H Pircher, C L Walker, E E Michalopoulos, F Rupp, H Hengartner, T W Mak
Journal: The Journal of Experimental Medicine (1987)

The primary structure of the alpha and beta chains of the T cell antigen receptor in four cytotoxic T cell clones specific for N-iodoacetyl-sulfonic-naphthyl-ethylene-diamine (AED)-haptenated target cells displaying a particular class I MHC molecule has been determined. Two of the T cell clones, 8/10-2 and 5/10-20K, recognize AED-modified targets in association with H-2Kb, while the other two clones 5/10-20D and C9 react with AED-modified cells in the context of H-2Db. Comparison of the nucleotide sequences of both the alpha and beta chain cDNAs and their deduced protein sequences indicates that a specific variable gene segment was not used to recognize the hapten and/or class I gene products. Furthermore, there does not appear to be any conserved amino acid residues used in the AED-specific response other than the framework amino acids. However, when the two clones 8/10-2 and 5/10-20D were compared, a striking similarity was seen in the J segments. These two clones that recognize AED in the context of different MHC epitopes used identical J alpha (J alpha 810) and J beta (J beta 2.6) gene segments. C9, specific for AED-Db, shared identical V beta (V beta 6) and J beta gene segments (J beta 1.1) as those of a cytotoxic T cell that recognizes allogeneic targets expressing Db. These data indicate that a simple rule governing the usage of the variable regions of either the alpha or beta T cell receptor (TcR) genes in the recognition of antigen and MHC gene products cannot be formulated. However, subtle similarities can be detected in some situations between the primary structures of the TcR and the targets they recognize.
A New Theory of Phylogeny Inference Through Construction of Multidimensional Vector Space
Authors: Yasuhiro Kitazoe, Yukio Kurihara, Yuichi Narita, Yoshiyasu Okuhara, Akira Tominaga, Tomohiko Suzuki
Journal: Molecular Biology and Evolution (2001)

Here, a new theory of molecular phylogeny is developed in a multidimensional vector space (MVS). The molecular evolution is represented as a successive splitting of branch vectors in the MVS. The end points of these vectors are the extant species and indicate the specific directions reflected by their individual histories of evolution in the past. This representation makes it possible to infer the phylogeny (evolutionary histories) from the spatial positions of the end points. Search vectors are introduced to draw out the groups of species distributed around them. These groups are classified according to the nearby order of branches with them. A law of physics is applied to determine the species positions in the MVS. The species are regarded as the particles moving in time according to the equation of motion, finally falling into the lowest-energy state in spite of their randomly distributed initial condition. This falling into the ground state results in the construction of an MVS in which the relative distances between two particles are equal to the substitution distances. The species positions are obtained prior to the phylogeny inference. Therefore, as the number of species increases, the species vectors can be more specific in an MVS of a larger size, such that the vector analysis gives a more stable and reliable topology. The efficacy of the present method was examined by using computer simulations of molecular evolution in which all the branch- and end-point sequences of the trees are known in advance. In the phylogeny inference from the end points with 100 multiple data sets, the present method consistently reconstructed the correct topologies, in contrast to standard methods. In applications to 185 vertebrates in the α-hemoglobin, the vector analysis drew out the two lineage groups of birds and mammals. A core member of the mammalian radiation appeared at the base of the mammalian lineage. Squamates were isolated from the bird lineage to compose the outgroup, while the other living reptilians were directly coupled with birds without forming any sister groups. This result is in contrast to the morphological phylogeny and is also different from those of recent molecular analyses.
Which patients do benefit from an implantable atrial defibrillator?
Authors: Werner Jung, Dietrich Pfeiffer, Christian Wolpert, Luciano Pizzulli, Wolfgang Fehske, Burghard Schumacher, Thorsten Lewalter, Heyder Omran, Thomas Korte, Berndt Lüderitz
Journal: Journal of the American College of Cardiology (1996)
Increased expression of RXRα in dementia: an early harbinger for the cholesterol dyshomeostasis?
Authors: Afia Akram, James Schmeidler, Pavel Katsel, Patrick R Hof, Vahram Haroutunian
Journal: Molecular Neurodegeneration (2010)

Cholesterol content of cerebral membranes is tightly regulated by elaborate mechanisms that balance the level of cholesterol synthesis, uptake and efflux. Among the conventional regulatory elements, a recent research focus has been nuclear receptors, a superfamily of ligand-activated transcription factors providing an indispensable regulatory framework in controlling cholesterol metabolism pathway genes. The mechanism of transcriptional regulation by nuclear receptors such as LXRs involves formation of heterodimers with RXRs. LXR/RXR functions as a sensor of cellular cholesterol concentration and mediates cholesterol efflux by inducing the transcription of key cholesterol shuffling vehicles namely, ATP-binding cassette transporter A1 (ABCA1) and ApoE.In the absence of quantitative data from humans, the relevance of expression of nuclear receptors and their involvement in cerebral cholesterol homeostasis has remained elusive. In this work, new evidence is provided from direct analysis of human postmortem brain gene and protein expression suggesting that RXRα, a key regulator of cholesterol metabolism is differentially expressed in individuals with dementia. Importantly, RXRα expression showed strong association with ABCA1 and ApoE gene expression, particularly in AD vulnerable regions.These findings suggest that LXR/RXR-induced upregulation of ABCA1 and ApoE levels may be the molecular determinants of cholesterol dyshomeostasis and of the accompanying dementia observed in AD.
Analysis of Efficacy and Safety in Patients Aged 65–75 Years at Randomization
Authors: H. Andrew W. Neil, David A. DeMicco, Don Luo, D. John Betteridge, Helen M. Colhoun, Paul N. Durrington, Shona J. Livingstone, John H. Fuller, Graham A. Hitman
Journal: Diabetes Care (2006)

OBJECTIVE—Rates of cardiovascular disease are highest in the elderly. Lipid-lowering statin therapy reduces the proportional risk as effectively in older patients as in younger individuals; however, limited data are available for elderly patients with type 2 diabetes. We conducted a post hoc analysis to compare the efficacy and safety of atorvastatin among 1,129 patients aged 65–75 years at randomization with 1,709 younger patients in the Collaborative Atorvastatin Diabetes Study (CARDS). RESEARCH DESIGN AND METHODS—CARDS was a randomized placebo-controlled trial of 10 mg/day atorvastatin for primary prevention of cardiovascular disease in patients aged 40–75 years with LDL cholesterol concentrations ≤4.14 mmol/l followed for a median of 3.9 years. The primary end point was time to first occurrence of acute coronary heart disease events, coronary revascularizations, or stroke. RESULTS—Atorvastatin treatment resulted in a 38% reduction in relative risk ([95% CI −58 to −8], P = 0.017) of first major cardiovascular events in older patients and a 37% reduction ([−57 to −7], P = 0.019) in younger patients. Corresponding absolute risk reductions were 3.9 and 2.7%, respectively (difference 1.2% [95% CI −2.8 to 5.3], P = 0.546); numbers needed to treat for 4 years to avoid one event were 21 and 33, respectively. All-cause mortality was reduced nonsignificantly by 22% ([−49 to 18], P = 0.245) and 37% ([−64 to 9], P = 0.98), respectively. The overall safety profile of atorvastatin was similar between age-groups. CONCLUSIONS—Absolute and relative benefits of statin therapy in older patients with type 2 diabetes are substantial, and all patients warrant treatment unless specifically contraindicated.
Intestinal Obstruction due to Occlusion of the Ileum by Pressure Band: Operation: Recovery
Authors: R. Jones
Journal: BMJ (1894)

was etithier incurablez, or at most yiel(le(l oily to somie magic iliarn or X eu tl the secret of whiheli wvas kivn but to a jew-mostly old womiien.In almost all the calses the stools liad been observed to be pale and clay-coloured, aiiI l genierally of stitl' consistenee.In some, however, there was (liarrll(ea, and in these the appear- ance would be deceptive.The colour of t}le Ur'iiie had also been noted in mnost cases.Suffice it to say that these were cases of jaundice, aiidl jaunidice in a coimiparatively simple form.I kept the patients oni milk diet.The medlicinal treatmenit I have already indicated.Ini no case did I fiind it necessary to confine them to bed.There was seldom any rise of teml)era- ture or quickeninig of the pulse.They were generally out of sorts for a week or ten days, but recovery was rapid anld coin- plete.WhIietlher the treatment adol)ted had muclh to do witlh the cure I am not at all certain, but of this I am satisied-that othler cases whiclh received no treatment, or at Imiost a dose of senna or castor oil, also recovered, and recovered ra idly.
PROTEASE-ACTIVATED RECEPTORS ARE EXPRESSED IN HUMAN TENDON TISSUE AND MAY EXPLAIN EXCESSIVE PAIN-SIGNALLING IN TENDINOPATHY
Authors: G Andersson, H Alfredson
Journal: British Journal of Sports Medicine (2013)

Introduction Several painful conditions throughout the human body—such as interstitial cystitis, Dupuytren's contracture, and complex regional pain syndrome—have been shown to exhibit tissues with an increase in mast cell population. One such painful condition—where the pain is not considered proportionate to the tissue changes—is tendinopathy. One study has shown that activation via protease-activated receptor 4 (PAR 4 ) can lead to an increased nociception in joints, and similar mechanisms may be at play in tendinopathy, where substances released by mast cells may activate the PARs. Mast cells are also known mediators of inflammatory responses to injury, but have also been found to regulate cell proliferation and vasodilation in certain tissues via PARs, and tendinopathies are known to exhibit tissue characteristics involving hypercellularity and vascular changes. The aim of this study was to determine whether tissues surrounding the Achilles tendon exhibit PAR 4 , as a basis for further studies on interactions between the tendon, vascularity and nerves, and the mast cell population found in tendinopathy tendons. Methods Biopsies of about 5×5 mm were taken from the ventral part of the Achilles tendon and the paratendinous tissues of this area, from two groups. One group consisted of patients suffering from mid-portion tendinopathy with tendinosis (n=8). Normal controls (n=2) donated biopsies from the same area. Both procedures were guided by ultrasound and performed through a minimal skin incision. These biopsies were later sectioned and immunocytochemistry was used to study the expression patterns of PAR 4 . Double-staining with PAR 4 and substance P (SP) was performed. Results The sections showed strong reactivity for PAR 4 in the blood vessels both in the tendon tissue proper as well as in the more abundant vascular areas ventral to the tendon in biopsies from both normal tendons and those from patients diagnosed with tendinosis. Tenocytes expressed PAR 4 to a varying degree (figure 1), with it being expressed more in cells with a rounded nuclei, primarily in tendons from the tendinosis group. PAR 4 was expressed on SP-positive nerve fibres in the paratendinous tissue (figure 2). Figure 1. (a) Tenocytes show reactions for PAR 4 (in red). Counterstained with DAPI. (b) Vessels positive for PAR 4 . Figure 2. (a) A nerve fibre and vessel positive for PAR4. In b the nerve fibre shows reactivity for substance P. Discussion These findings give basis for further studies into the interactions of SP-positive nerves and mast cells in tendon pathology. Earlier studies have shown regulation of vascular permeability and dilation, as well as fibroblast proliferation through activation of PARs. The PAR 4 may, through activation of proteases released from mast cells, to some extent be responsible not only for tenocyte proliferation and vascular regulation, but also for an enhanced pain signalling in tendinopathy through SP-positive afferents.
Polyarteritis nodosa and mixed cryoglobulinaemia related to hepatitis B and C virus coinfection
Authors: P G. d. L. P. Lefebvre
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To determine the responsibility of hepatitis B virus (HBV) and hepatitis C virus (HCV) and therapeutic implications in a patient who developed systemic vasculitis. <h3>CASE REPORT</h3> The case of a 38 year old woman who had a past history of addiction to intravenous drugs and developed systemic vasculitis after infection by HBV and HCV is described. The clinical and laboratory findings substantiated not only the diagnosis of polyarteritis nodosa (PAN) but also that of mixed cryoglobulinaemia with a monoclonal IgMκ component. <h3>CONCLUSION</h3> Because cryoglobulins are rarely found in HBV related PAN but often associated with HCV infection, and in light of the histological findings, cryoglobulinaemia was interpreted as being secondary to HCV infection. This example of a highly complex situation emphasises the need to gather all relevant clinical, biological, histological, and complementary data so that the best treatment for overlapping of distinct vasculitides can be selected.
Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1-deficient mice
Authors: Hiroo Yamaguchi, Jie Shen
Journal: Molecular Neurodegeneration (2007)

Parkinson's disease is the most common movement disorder characterized by dopaminergic dysfunction and degeneration. Loss-of-function mutations in the DJ-1 gene have been linked to autosomal recessive forms of early-onset familial Parkinson's disease. DJ-1 is thought to play roles in protection of cells against oxidative stress and in maintenance of the normal dopaminergic function in the nigrostriatal pathway. Here we investigate the consequence of both DJ-1 inactivation and aging in mice. We found that DJ-1-/- mice at the age of 24-27 months have normal numbers of dopaminergic neurons in the substantia nigra and normal levels of dopamine and its major metabolites in the striatum. The number of noradrenergic neurons in the locus coeruleus is also unchanged in DJ-1-/- mice. Moreover, there is no accumulation of oxidative damage or inclusion bodies in aged DJ-1-/- brains. Together, these results indicate that loss of DJ-1 function alone is insufficient to cause nigral degeneration and oxidative damage in the life span of mice.
THE RÔLE OF COLLOID AND OF SALINE IN THE TREATMENT OF SHOCK 12
Authors: A. W. Winkler, T. S. Danowski, J. R. Elkinton
Journal: Journal of Clinical Investigation (1946)

The effects of intravenous saline in early salt- depletion shock in dogs have been described in previous reports (1, 2).Cardiac output and blood pressure recovered considerably or completely from their depressed levels, plasma volume rapidly reexpanded, and protein which had disappeared earlier returned to the circulating plasma.Intra- venous glucose solutions were much less effective in correcting the depression in hemodynamic status and in restoring the deficit of circulating plasma protein.Since a deficit of plasma protein was an almost invariable accompaniment of acute salt-depletion shock, experiments were un- dertaken to determine whether the administration of serum or gelatin would produce a hemodynamic effect greater than that of saline alone. MATERIALS AND METHODSAdult fasting female dogs were used throughout.*The methods by which salt depletion was induced and by which cardiac output, blood pressure, circulation time, relative plasma volume, and change in circulating plasma protein were measured have been described (1).In 3 experiments essentially salt-free gelatin or serum was administered.8In 4 experiments therapy consisted of the injection of 130 to 300 ml. of serum or gelatin solution containing 0.9 per cent sodium chloride.This procedure replaced only 11 to 36 per cent of the salt deficit.In 2 experiments serum or gelatin was imme- diately followed by the administration of 5.0 per cent sodium chloride solution, and in 1 experiment by 0.9 per cent sodium chloride solution, in amounts sufficient to replace the entire salt deficit.
Controlled trials testing two or more treatments simultaneously
Authors: R. Doll
Journal: Journal of the Royal Society of Medicine (2005)

In 1950, when I started clinical research in gastroenterology, the treatment of gastric ulcers was far from satisfactory. The role of Helicobacter pylori had not been discovered and the symptoms, although they could be relieved, kept on recurring irrespective of treatment and often eventually became so severe that the ulcer had to be resected with much of the acid secreting part of the stomach.

Orthodox treatment consisted of five elements, which were combined with varying emphasis, depending on the views of the individual physicians. All of them prescribed alkalis for the relief of pain and all of them recommended bed rest if symptoms persisted. Nearly all advised a bland diet, varying from 2-hourly milk feeds to a convalescent diet that excluded fried foods, pastry, various meats, and raw vegetables. Nearly all sought to treat the postulated underlying emotional factors by discussion, reassurance, and a sedative. Lastly, in an attempt to reduce acid secretion and inhibit gastric tone, many also prescribed atropine or one of its synthetic analogues.

To this schedule there was often added some new treatment that became popular for a while before being replaced by another: I had no difficulty in drawing up a list of remedies beginning with each letter of the alphabet. If, therefore, any substantial proportion of even the most promising remedies were to be properly evaluated it would take a very long time, so there would be considerable advantage in testing two or more in the same group of patients.
Prevalence of Anaplasma species and habitat suitability for ticks in Sicily
Authors: A. Torina, A. Alongi, V. Naranjo, A. Estrada-Peña, J. Vicente, S. Scimeca, A.M.F. Marino, F. Salina, S. Caracappa, J. de la Fuente
Journal: Clinical Microbiology and Infection (2009)