tbuckley/cabot-search huggingface dataset:
Big brains as shelters for odd genes: How fast does complex behavior evolve?
Authors: H.-P. Lipp
Journal: Behavioral and Brain Sciences (2000)

Laland et al. suggest that as a specific evolutionary force niche construction has entailed the encephalization of the brain. While not denying rapid co-evolution of brain traits and abilities with niches and cultures, I argue that encephalization reflects a classical genetic buffer system allowing rapid evolutionary adaptation independent of the nature of the selective pressure.
Hemodynamic efficacy of the new resolution clip device in comparison with high-volume injection therapy in spurting bleeding: a prospective experimental trial using the compactEASIE simulator
Authors: J. Maiss, C. Baumbach, Y. Zopf, A. Naegel, M. Wehler, T. Bernatik, E. Hahn, D. Schwab
Journal: Endoscopy (2006)

Background and study aims: Peptic ulcers are the most frequent cause of gastrointestinal bleeding. The use of hemoclips has become established as an effective form of treatment in addition to injection therapy. However, hemoclips have not previously been compared with injection therapy in an experimental setting using objective parameters. Materials and methods: In a prospective, randomized, and controlled trial, the disposable Resolution hemoclip device (Boston Scientific, n = 40) was compared with conventional injection therapy (n = 40) in an experimental setting, using the compactEASIE simulator equipped with an upper gastrointestinal organ package to simulate bleeding. Four investigators with different levels of endoscopic experience participated in the study. On a randomized basis, each investigator treated 20 bleeding sites either by applying one clip (n = 10) or by carrying out high-volume four-quadrant injection (4 × 10 ml saline) of a spurting vessel. The efficacy of the hemostasis was assessed by continuous measurement of pressure within the afferent vessel before and after clip application or injection therapy and calculating the relative reduction in the vessel’s diameter with each treatment method. The system pressure was recorded 1 min before and 1 min after treatment. The ease of application of each method was rated by the endoscopist and by the assisting nurse using a visual analogue scale (0 - 100, with 100 being best). Results: All of the 40 hemoclipping and injection treatments were carried out successfully. Both methods led to a significant increase in peak pressure (Resolution clip 71.8 ± 66.8 mm Hg, P < 0.001; injection 71.9 ± 53.8 mm Hg, P < 0.001), representing a significant relative reduction in the vessel diameter. There were no significant differences in peak pressure between the two treatments (P = 0.995). The mean increase in pressure during the first minute after the intervention (clip 49.3 ± 67.0 mm Hg vs. injection 19.9 ± 41.6 mm Hg) was significantly greater with the hemoclipping procedure (P = 0.021). More experienced investigators achieved a greater increase in system pressure, but the difference was not significant. The assessments of the ease of application by the assistants (84 ± 13) and endoscopists (86 ± 16) did not show any significant differences (P = 0.402) for the clipping device. Conclusions: No significant differences between the two treatment methods were detected with regard to the immediate efficacy of hemostasis. However, long-term hemostasis was better with hemoclipping. The endoscopist’s level of experience also appears to play a role, particularly when hemoclips are used.
Questions for research
Authors: F. Godlee
Journal: BMJ (2010)

Continuing last week’s focus on the BMJ ’s research papers ( BMJ 2009;339:b5632, doi:10.1136/bmj.b5632) it’s gratifying to see them performing so well in Journal Watch ’s first ever listing of the medical stories that were most read in the past year.

Journal Watch , run by the Massachusetts Medical Society, which owns the New England Journal of Medicine , gets its team of contributors to summarise what they see as the most interesting and important articles published in each field. Now Journal Watch has also summed up readers’ choices during 2009. BMJ research articles feature more than those from any other general …
Loss of heparan sulfate glycosaminoglycan assembly in podocytes does not lead to proteinuria
Authors: Shoujun Chen, Deborah J. Wassenhove-McCarthy, Yu Yamaguchi, Lawrence B. Holzman, Toin H. van Kuppevelt, Guido J. Jenniskens, Tessa J. Wijnhoven, Ann C. Woods, Kevin J. McCarthy
Journal: Kidney International (2008)
The substantia nigra is a major target for neurovirulent influenza A virus.
Authors: M Takahashi, T Yamada, S Nakajima, K Nakajima, T Yamamoto, H Okada
Journal: The Journal of Experimental Medicine (1995)

Clinical and immunohistochemical studies were done for 3-39 d on mice after intracerebral inoculation with the neurovirulent A/WSN/33 (H1N1; WSN) strain of influenza A virus, the nonneurovirulent A/Aichi/2/68 (H3N2; Aichi) strain, and two reassortant viruses between them. The virus strains with the WSN gene segment coding for neuraminidase induced meningoencephalitis in mice. The mice inoculated with the R96 strain, which has only the neuraminidase gene from the WSN strain, had mild symptoms and weak positive immunostaining to the anti-WSN antibody in meningeal regions. Both the WSN and R404BP strains, which contain the WSN gene segments coding for neuraminidase and matrix protein, were clearly neurovirulent both clinically and pathologically. On day 3 after inoculation with either of these two strains, WSN antigen was detected in meningeal and ependymal areas, neurons of circumventricular regions, the cerebral and cerebellar cortices, the substantia nigra zona compacta, and the ventral tegmental area. On day 7, meningeal reactions and neuronal staining were still seen, and advanced accumulation of the viral antigen was evident in the substantia nigra zona compacta and hippocampus. Double immunostaining demonstrated that the WSN antigen was only seen in neurons and not in microglia or reactive astrocytes. Immunostaining for the lectin maackia amurensis agglutinin, which recognizes the Neu5Ac alpha 2,3 Gal sequence, which serves as a binding site for influenza A virus on target cell membranes, showed that positive staining was localized in the ventral substantia nigra and hippocampus. These results suggest that neurovirulent influenza A viruses could be one of the causative agents for postencephalitic parkinsonism.
Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial
Authors: Y Levy, C Capitant, S Houhou, I Carriere, JP Viard, C Goujard, JA Gastaut, E Oksenhendler, L Boumsell, E Gomard, C Rabian, L Weiss, JG Guillet, JF Delfraissy, JP Aboulker, M Seligmann
Journal: The Lancet (1999)
An Analysis of Morning Report: Implications for Internal Medicine Education
Authors: Neil S. Wenger
Journal: Annals of Internal Medicine (1993)

Objective: To compare the initial diagnosis of cases presented at morning report with the final morning report diagnosis reached at discharge from the Medicine service and the diagnosis as evaluated 6 months after discharge. Design: Prospective cohort study of morning report cases. Setting: A university internal medicine residency program. Measurements: Proportion of morning report cases in which the initial morning report diagnosis differed from the final morning report diagnosis at discharge or, in cases where a firm diagnosis was not reached at discharge, the proportion for which a diagnosis was established by 6 months after discharge. Main Results: In 24% of cases, a firm morning report diagnosis was not available at discharge. For 61% of these, a diagnosis could be established by 6-month follow-up: for 36% the diagnosis differed from the final morning report diagnosis; and for 25% it was the same. Among cases where a firm final diagnosis was reached during morning report, the initial morning report diagnosis differed for 17%. Conclusions: Most patients discharged without a firm diagnosis have one established by 6 months lateroften with surprising results. Postdischarge follow-up information could enhance the educational value of inpatient cases.
VLA-4-fibronectin interaction is required for the terminal differentiation of human bone marrow cells capable of spontaneous and high rate immunoglobulin secretion.
Authors: E Roldán, A García-Pardo, J A Brieva
Journal: The Journal of Experimental Medicine (1992)

Human bone marrow (BM) is a relevant site for immunoglobulin (Ig) generation in vivo. The occurrence of BM cells capable of spontaneous and high rate Ig secretion for 14 d in vitro has been described previously. Accordingly, these cells provide a suitable model for studying terminal B cell maturation within the BM. We have reported recently that these BM cells are not totally differentiated when isolated from the body, as they require inductive signals from adherent stromal BM cells to complete their maturation. Interleukin (IL)-6 produced by these adherent BM cells was identified as one such signal. The present work shows that IL-6 was necessary, but not sufficient, for the induction of BM Ig-secreting cells, since the cytokine was unable to restore missing IgG in nonadherent BM cell cultures. Supernatants (SN) obtained from cultures of stromal adherent BM cells, either freshly isolated or derived from long-term BM culture (LTBMC), restored Ig secretion by nonadherent BM cells, suggesting that additional soluble factors from BM stromal cells were required. Fibronectin (FN) was identified as that factor, as can be deduced from the following findings: (a) stromal, but not nonadherent, BM cells constitutively produced FN; (b) anti-FN antibodies markedly reduced the IgG secretion in cultures of BM mononuclear cells (BMMC), and blocked the inductive effect of stromal cell SN on nonadherent BM cells, and such a blockade could be reversed by exogenous FN; and (c) finally, although neither IL-6 nor FN alone exerted any effect, the combination of both factors induced optimal Ig secretion by nonadherent BM cells. Furthermore, VLA-4 molecules seemed to be the FN receptor that was active in this culture system, as indicated by: (a) BM Ig-secreting cells exhibited the phenotype VLA-4+ VLA-5-; (b) mAbs directed to VLA-4 (anti-CD29 and anti-CD49d), but not those directed to other adhesion molecules, inhibited Ig secretion by BMMC cultures, and this effect was reversed by FN; (c) the inductive role of the entire FN molecule could be replaced by a fragment containing the CS-1 region, but not by a fragment containing the RGDS sequence; and (d) only mAbs anti-CD49d capable of blocking VLA-4-FN interaction inhibited induction by either the FN or the CS-1-containing fragment of FN.(ABSTRACT TRUNCATED AT 400 WORDS)
Intravenous immunoglobulins induce CD32-mediated platelet aggregation<i>in vitro</i>
Authors: A. Pollreisz, A. Assinger, S. Hacker, K. Hoetzenecker, W. Schmid, G. Lang, M. Wolfsberger, B. Steinlechner, E. Bielek, E. Lalla, W. Klepetko, I. Volf, H.J. Ankersmit
Journal: British Journal of Dermatology (2008)

Background Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side‐effect of their application is intravascular thrombosis, which is thought to be related to pre‐existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32). Objectives To investigate if IVIg and CMVIg have the potential to cause CD32‐dependent platelet aggregation. Methods The influence of CMVIg or IVIg on platelets pre‐incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence‐activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme‐linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low‐affinity Fc IgG receptor (CD32). Conclusions Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.
Retrospective time-trend study of polybrominated diphenyl ether and polybrominated and polychlorinated biphenyl levels in human serum from the United States.
Authors: Andreas Sjödin, Richard S Jones, Jean-François Focant, Chester Lapeza, Richard Y Wang, Ernest E McGahee, Yalin Zhang, Wayman E Turner, Bill Slazyk, Larry L Needham, Donald G Patterson
Journal: Environmental Health Perspectives (2004)

Six polybrominated diphenyl ethers (PBDEs), one hexabromobiphenyl [polybrominated biphenyl (PBB)], and one hexachlorobiphenyl [polychlorinated biphenyl (PCB)] were measured in 40 human serum pools collected in the southeastern United States during 1985 through 2002 and in Seattle, Washington, for 1999 through 2002. The concentrations of most of the PBDEs, which are commercially used as flame retardants in common household and commercial applications, had significant positive correlations with time of sample collection, showing that the concentrations of these compounds are increasing in serum collected in the United States. In contrast, PCB and PBB levels were negatively correlated with sample collection year, indicating that the levels of these compounds have been decreasing since their phaseout in the 1970s.
Renal Hemodynamics and Plasma Renin Activity after Renal Artery Constriction in Conscious Dogs
Authors: Robert C. Harris, Carlos R. Ayers
Journal: Circulation Research (1972)

Renal hemodynamics and plasma renin activity were studied during acute and chronic renal artery constriction produced by an externally controlled snare in conscious dogs. Renal vascular resistance immediately decreased, then increased to a level above control after approximately 1 hour, and continued to increase until the second day after constriction. Total renal flow rate was unchanged in the first hour, decreased in the second hour, and decreased further between the first and the second day after constriction. Renal artery pressure distal to the snare increased after the initial stenosis but remained below the control level. Changes in renal artery pressure were dependent primarily on renal vascular resistance rather than on aortic blood pressure. Analysis of 133 Xe-clearance curves showed that the fractional weight of and the fractional flow to the fastest-clearing compartment decreased after the first hour and decreased further between the first and the second day after constriction. Plasma renin activity rose immediately, began to drop on the first day after constriction, and was essentially normal by the second day. No parameter changed significantly after the second day, and no hemodynamic factor was consistently correlated with changes in plasma renin activity. These results do not confirm an apparent correlation between renal vasodilation and renin release reported in an earlier study.
Health-Related Quality of Life and Sorafenib
Authors: Giancarlo Spinzi, Natalia Terreni
Journal: Hepatology (2010)

I read the very interesting article by Finn1 about sorafenib, the first systemic agent showing a survival advantage when it is used to treat patients with hepatocellular carcinoma. Finn1 pointed out common and predictable toxicities, including hand-skin reactions, anorexia, and diarrhea, which were experienced by 15% to 40% of the treated patients. However, Finn1 did not mention the importance of health-related quality of life (HRQOL) with respect to the potential side effects of hepatocellular carcinoma treatment and wrote only a few words about the cost of the drug. The growth of health care costs continues to outpace our ability to pay for health care in the future. We need to know not only the clinical efficacy of the drug but also its cost-effectiveness and the HRQOL of patients randomized between a placebo and sorafenib. Studies of HRQOL may add value in a variety of ways, including the provision of data that may contrast with or support the primary outcome and sometimes change a study's interpretation. Studies of cost-effectiveness and HRQOL may provide valuable sources of additional information useful to both the clinician and the patient when treatment decisions are being made, and they are considered important endpoints together with traditional measures.2 I think that their assessment is particularly worthwhile for trials in which survival rates are low. Natalia Terreni M.D.*, Giancarlo Spinzi M.D.*, * Division of Gastroenterology, Valduce Hospital, Como, Italy.
Unbalanced excitability underlies offline reactivation of behaviorally activated neurons
Authors: Mika Mizunuma, Hiroaki Norimoto, Kentaro Tao, Takahiro Egawa, Kenjiro Hanaoka, Tetsuya Sakaguchi, Hiroyuki Hioki, Takeshi Kaneko, Shun Yamaguchi, Tetsuo Nagano, Norio Matsuki, Yuji Ikegaya
Journal: Nature Neuroscience (2014)
Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease
Authors: Michiharu Komatsu, Masahide Yazaki, Naoki Tanaka, Kenji Sano, Etsuko Hashimoto, Yo-ichi Takei, Yuan-Zong Song, Eiji Tanaka, Kendo Kiyosawa, Takeyori Saheki, Toshifumi Aoyama, Keiko Kobayashi
Journal: Journal of Hepatology (2008)
Marijuana as Medicine-Reply
Authors: Lester Grinspoon
Journal: JAMA (1995)

<h3>In Reply.</h3> —As Dr Lowenthal points out, the contrast between tobacco policies and marijuana policies is instructive in more ways than one. Dr Bennetts raises the issues of social acceptability, cost, and alternatives. His fear that medical availability would lead to more nonmedical use is unwarranted. Cocaine and morphine, for example, have always been available as prescription drugs, but no one believes that availability is a significant cause of illicit use. On the issue of cost, it is important to point out that marijuana is less expensive than many of the medicines it could replace. As for the question of alternatives, of course we have no objection to advocacy for other orphan drugs and nonchemical approaches. Dr Nahas and Manger are wrong in their assertion that all the pharmacological properties of marijuana are attributable to THC. One reason most patients prefer smoked marijuana to oral dronabinol<sup>1(p39)</sup>is the powerful
"THE COFFEY-HUMBER PATENT"
Authors: Thomas E. Robertson
Journal: JAMA (1931)

<h3>To the Editor:</h3> —I have read with interest Dr. Rehfisch's letter relative to the Coffey-Humber patent (The Journal, March 7, p. 794). After Dr. Rehfisch had complimented the Patent Office onthe "masterly report on Coffey's preposterous claims, which were annihilated one by one by a patent examiner who dealt with them in a truly scientific fashion," he might have been sufficiently generous to give the examiner who wrote such a "masterly report" the credit for properly considering the application before he would grant the patent. An investigation shows that Dr. Rehfisch was entirely in error in his belief that there was such great speed that the case was resubmitted one day and granted the next without due deliberation on the part of the examiner. Patent Office Rule 13 permits an applicant or his attorney to interview an examiner after rejection and to go over the entire case orally as with
Marmoset phylogenetics, conservation perspectives, and evolution of the mtDNA control region
Authors: C. H. Tagliaro, M. P. Schneider, H. Schneider, I. C. Sampaio, M. J. Stanhope
Journal: Molecular Biology and Evolution (1997)

Marmosets (genus Callithrix) are a diverse group of platyrrhine primates with 13-15 purported taxa, many of them considered endangered. Morphological analyses constitute most of the basis for recognition of these forms as distinct taxa. The purpose of this study was to provide a molecular view, based on mitochondrial control region sequences, of the evolutionary history of the marmosets, concomitant with a molecular phylogenetic perspective on species diversity within the group. An additional purpose was to provide the first comparative examination of a complete New World monkey control region sequence with those of other mammals. The phylogenetic analyses provide convincing support for a split between the Atlantic forest and Amazonian marmosets, with the inclusion of the pygmy marmoset (Cebuella pygmaea) at the base of the Amazonian clade. The earliest branch of the Atlantic forest group was C. aurita. In the Amazonian group, the analyses do not support the recognition of C. humeralifer and the recently described C mauesi as distinct taxa. They do, however, support a clear distinction between C. argentata and a strongly supported mixed clade of C. humeralifer and C. mauesi. In the Atlantic forest group, the phylogenetic tree suggests mixing between C. penicillata, C. kuhli, and possibly C. jacchus. Most of the sequence features characteristic of other mammal control regions were also evident in marmosets, with the exception that conserved sequence blocks (CSBs) 2 and 3 were not clearly identifiable. Tandem repeat units often associated with heteroplasmy in a variety of other mammals were not evident in the marmoset sequences.
Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of hepatocellular damage and response to interferon treatment in patients with chronic hepatitis C.
Authors: G Ballardini, P Groff, P Pontisso, F Giostra, R Francesconi, M Lenzi, D Zauli, A Alberti, F B Bianchi
Journal: Journal of Clinical Investigation (1995)

To obtain information on the mechanisms of hepatocellular damage and the determinants of response to interferon, hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C and intercellular adhesion-1 molecules, and the number of lobular T lymphocytes were studied in 38 anti-HCV-positive patients. 14 patients did not show a primary response to interferon treatment. HCV genotype 1b was detected in 11 of them. They displayed higher scores of HCV-positive hepatocytes, HLA-A,B,C, and ICAM-1 molecules expression than with the responders. HCV-infected hepatocytes maintained the capacity to express HLA-A,B,C and ICAM-1 molecules. CD8-positive T cells in contact with infected hepatocytes and Councilman-like bodies were observed. A significant correlation was found between the number of lobular CD8-positive T cells and alanine amino transferase levels. No differences were observed in clinical, biochemical, and histological features between patients with high and low number of hepatocytes containing HCV antigens. These data suggest a prominent role of T cell-mediated cytotoxicity in the genesis of hepatocellular damage. The high expression of interferon-inducible antigens like HLA-A,B,C molecules suggests the presence of strong activation of the interferon system possibly related to high HCV replication in nonresponder patients infected with genotype 1b.