tbuckley/cabot-search huggingface dataset:
Factors in resistance to and recovery from M. pulmonis-induced arthritis in mice.
Authors: G Taylor, D Taylor-Robinson
Journal: Annals of the Rheumatic Diseases (1977)

A previous infection of C3H mice with viable Mycoplasma pulmonis organisms protected them from arthritis induced by intravenous inoculation of these organisms, whether or not their initial arthritis had resolved at the time of challenge. Although spleen cells obtained from such animals conferred resistance to acute arthritis in syngeneic recipient mice, convalescent-phase serum was much more effective in this respect. In addition, the transfer of 9immune9 spleen cells to M. pulmonis-infected mice treated with cyclophosphamide did not prevent them from dying, whereas the transfer of convalescent-phase serum to such animals reduced the incidence of mortality. Since M. pulmonis organisms are rapidly inactivated in mice treated with convalescent-phase serum it is suggested that the transferred serum may act by promoting phagocytosis of the mycoplasmas. Although the reason for some mice developing a prolonged arthritis is not clear, the results show that humoral immune mechanisms are more important than cell-mediated ones in preventing acute arthritis and that the humoral mechanisms are of greater importance than the cell-mediated in resistance to and recovery from a generalized mycoplasma infection.
New vascular classification of port‐wine stains: improving prediction of Sturge–Weber risk
Authors: R. Waelchli, S.E. Aylett, K. Robinson, W.K. Chong, A.E. Martinez, V.A. Kinsler
Journal: British Journal of Dermatology (2014)

Facial port‐wine stains (PWSs) are usually isolated findings; however, when associated with cerebral and ocular vascular malformations they form part of the classical triad of Sturge–Weber syndrome (SWS). To evaluate the associations between the phenotype of facial PWS and the diagnosis of SWS in a cohort with a high rate of SWS. Records were reviewed of all 192 children with a facial PWS seen in 2011–13. Adverse outcome measures were clinical (seizures, abnormal neurodevelopment, glaucoma) and radiological [abnormal magnetic resonance imaging (MRI)], modelled by multivariate logistic regression. The best predictor of adverse outcomes was a PWS involving any part of the forehead, delineated at its inferior border by a line joining the outer canthus of the eye to the top of the ear, and including the upper eyelid. This involves all three divisions of the trigeminal nerve, but corresponds well to the embryonic vascular development of the face. Bilateral distribution was not an independently significant phenotypic feature. Abnormal MRI was a better predictor of all clinical adverse outcome measures than PWS distribution; however, for practical reasons guidelines based on clinical phenotype are proposed. Facial PWS distribution appears to follow the embryonic vasculature of the face, rather than the trigeminal nerve. We propose that children with a PWS on any part of the 'forehead' should have an urgent ophthalmology review and a brain MRI. A prospective study has been established to test the validity of these guidelines.
Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell–mediated deletion
Authors: Dimitra Peppa, Upkar S. Gill, Gary Reynolds, Nicholas J.W. Easom, Laura J. Pallett, Anna Schurich, Lorenzo Micco, Gaia Nebbia, Harsimran D. Singh, David H. Adams, Patrick T.F. Kennedy, Mala K. Maini
Journal: The Journal of Experimental Medicine (2012)

Antiviral T cell responses in hepatotropic viral infections such as hepatitis B virus (HBV) are profoundly diminished and prone to apoptotic deletion. In this study, we investigate whether the large population of activated NK cells in the human liver contributes to this process. We show that in vitro removal of NK cells augments circulating CD8+ T cell responses directed against HBV, but not against well-controlled viruses, in patients with chronic hepatitis B (CHB). We find that NK cells can rapidly eliminate HBV-specific T cells in a contact-dependent manner. CD8+ T cells in the liver microcirculation are visualized making intimate contact with NK cells, which are the main intrahepatic lymphocytes expressing TNF-related apoptosis-inducing ligand (TRAIL) in CHB. High-level expression of the TRAIL death receptor TRAIL-R2 is found to be a hallmark of T cells exposed to the milieu of the HBV-infected liver in patients with active disease. Up-regulation of TRAIL-R2 renders T cells susceptible to caspase-8–mediated apoptosis, from which they can be partially rescued by blockade of this death receptor pathway. Our findings demonstrate that NK cells can negatively regulate antiviral immunity in chronic HBV infection and illustrate a novel mechanism of T cell tolerance in the human liver.
Susceptibility to Myocarditis Is Dependent on the Response of αβ T Lymphocytes to Coxsackieviral Infection
Authors: Mary Anne Opavsky, Josef Penninger, Karen Aitken, Wen-Hu Wen, Fayez Dawood, Tak Mak, Peter Liu
Journal: Circulation Research (1999)

Abstract —Viral myocarditis is an important cause of heart failure and dilated cardiomyopathy. T lymphocytes are implicated in myocardial damage in murine models of coxsackievirus B3 (CVB3) myocarditis. We used knockout mice lacking CD4 (CD4 −/− ), CD8 (CD8 −/− ), both coreceptors (CD4 −/− CD8 −/− ), or the T-cell receptor β chain (TCRβ −/− ) to address the contribution of T-cell subpopulations to host susceptibility to CVB3 myocarditis. Severity of disease was magnified in CD8 −/− mice but attenuated in CD4 −/− mice, consistent with a pathogenic role for CD4 + lymphocytes. Elimination of both CD4 and CD8 molecules from T lymphocytes by genetic knockout better protected mice from myocarditis, demonstrating that both CD4 + and CD8 + T cells contribute to host susceptibility. The same benefit occurred in TCRβ −/− mice, with prolonged survival and minimal myocardial disease observed after CVB3 infection. Elevated interferon-γ and decreased tumor necrosis factor-α expression are associated with attenuated myocardial damage in CD4 −/− CD8 −/− mice. These results show that the presence of TCRαβ + T cells enhances host susceptibility to myocarditis. The severity of myocardial damage and associated mortality are dependent on the predominant T-cell type available to respond to CVB3 infection. One mechanism by which CD4 + and CD8 + T-cell subsets influence the pathogenesis of myocarditis may involve specific cytokine expression patterns.
Incomplete Relaxation between Beats after Myocardial Hypoxia and Ischemia
Authors: Myron L. Weisfeldt, Paul Armstrong, Hugh E. Scully, Charles A. Sanders, Willard M. Daggett
Journal: Journal of Clinical Investigation (1974)

Recovery from hypoxia has been shown to prolong cardiac muscle contraction, particularly the relaxation phase. The present studies were designed to examine whether incomplete relaxation between beats can result from this prolongation of contraction and relaxation in isolated muscle after hypoxia and in the canine heart after both hypoxia and acute ischemia. The relationship between heart rate and the extent of incomplete relaxation is emphasized in view of the known enhancement of the velocity of contraction caused by increasing heart rate. The extent of incomplete relaxation during 10-s periods of pacing at increasing rates was examined before and after hypoxia in isometric cat right ventricular papillary muscle (12-120 beats/min) and in the canine isovolumic left ventricle (120-180 beats/min). Incomplete relaxation was quantified by measuring the difference between the lowest diastolic tension or pressure during pacing and the true resting tension or pressure determined by interruption of pacing at each rate. In eight cat papillary muscles (29 degrees C), there was significantly greater incomplete relaxation 5 min after hypoxia at rates of 96 and 120 beats/min (P < 0.02 vs. before hypoxia). In seven canine isovolumic left ventricles, recovery from hypoxia and higher heart rates also resulted in incomplete relaxation. Incomplete relaxation before hypoxia at a rate of 180 beats/min was 0.8+/-0.5 cm H(2)O and at 5 min of recovery from hypoxia was 12.6+/-3.5 cm H(2)O (P < 0.01). 12 hearts were subjected to a 1.5-3-min period of acute ischemia and fibrillation. There was significant incomplete relaxation at a rate of 140 beats/min for 5 min after defibrillation and reperfusion. These data indicate that incomplete relaxation is an important determinant of diastolic hemodynamics during recovery from ischemia or hypoxia. The extent of incomplete relaxation appears to be a function of the rate of normalization of the velocity of relaxation and tension development after ischemia or hypoxia, the heart rate, and the magnitude of developed tension or pressure.
Morphine Use after Combat Injury in Iraq and Post-Traumatic Stress Disorder
Authors: Troy Lisa Holbrook, Michael R. Galarneau, Judy L. Dye, Kimberly Quinn, Amber L. Dougherty
Journal: New England Journal of Medicine (2010)

Post-traumatic stress disorder (PTSD) is a common adverse mental health outcome among seriously injured civilians and military personnel who are survivors of trauma. Pharmacotherapy in the aftermath of serious physical injury or exposure to traumatic events may be effective for the secondary prevention of PTSD.We identified 696 injured U.S. military personnel without serious traumatic brain injury from the Navy-Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database. Complete data on medications administered were available for all personnel selected. The diagnosis of PTSD was obtained from the Career History Archival Medical and Personnel System and verified in a review of medical records.Among the 696 patients studied, 243 received a diagnosis of PTSD and 453 did not. The use of morphine during early resuscitation and trauma care was significantly associated with a lower risk of PTSD after injury. Among the patients in whom PTSD developed, 61% received morphine; among those in whom PTSD did not develop, 76% received morphine (odds ratio, 0.47; P<0.001). This association remained significant after adjustment for injury severity, age, mechanism of injury, status with respect to amputation, and selected injury-related clinical factors.Our findings suggest that the use of morphine during trauma care may reduce the risk of subsequent development of PTSD after serious injury.
Microbial flora of the trachea during intubation of patients undergoing upper abdominal surgery.
Authors: J P Dilworth, R J White, E M Brown
Journal: Thorax (1992)

BACKGROUND: The presence of Haemophilus influenzae in the oropharynx is correlated with the subsequent development of chest infection. The importance of colonisation of the trachea by bacteria at the time of surgery is uncertain. This study investigated the tracheal flora at the time of intubation in 24 patients undergoing elective upper abdominal surgery. METHODS: The bacterial flora of the trachea was sampled in all 24 patients immediately after intubation and immediately before extubation. Patients were assessed postoperatively for the development of chest infection. RESULTS: Bacteria, including H influenzae in five cases, were isolated from the post-intubation brushings of the trachea of 15 patients. The pre-extubation brushings from only four patients yielded growth. Three of five patients developing a chest infection were colonised by H influenzae according to the postintubation brush, compared with two of 19 without chest infections. Before extubation two of five developing chest infections had H influenzae in the trachea but none of 19 without infection. All but one of the patients from whom H influenzae was isolated were smokers. CONCLUSIONS: These results suggest that the increased risk of postoperative chest infection in cigarette smokers may be due in part to colonisation of the trachea by H influenzae at the time of operation.
Management of soft tissue injury of hand wrist and elbow in sports
Authors: Alok Mishra
Journal: British Journal of Sports Medicine (2010)

A large number of sports injuries are inflicted on hand, wrist, forearm and elbow. Some injuries are due to overuse and chronic trauma. They are elusive. Pathology is friction stress and ischaemia. Protocol of management and understanding of pathology will help manage dancers and sports persons better. Soft tissue injury of hand wrist and forearm Most sports injuries are obvious and direct. Those due to overuse are elusive and insidious. They are mainly seen in sportspersons and dancers. Friction stress and ischaemia are main causes of overuse trauma in sportspersons. A tendon of strong athletic muscle or bursa may, during joint movement, be subjected to excessive friction in fibrous sheath or over a bony prominence. An inflammatory reaction starts up swelling occurs gliding movement is restricted in long tendons of hand. Repeated or unguarded strong athletic stress in hand and forearm may result in tears of muscle tendon and microfractures of bone. Excessive force sometimes causes complete of tendon or muscle. Muscle, which is firmly enclosed in fascial compartments of the forearm, become ischaemic, which may be relative arising only when excessive activity makes demands on the blood supply that cannot be met or absolute when intramuscular oedema causes swelling in a tight compartment with rampant use of crepe and other pressure bandages in hand and forearm causing further damage leading to ischaemic myositis. VIC protocol of preseason conditioning to postseason rehabilitation will be detailed in the presentation.
IRF8 Regulates Acid Ceramidase Expression to Mediate Apoptosis and Suppresses Myelogeneous Leukemia
Authors: Xiaolin Hu, Dafeng Yang, Mary Zimmerman, Feiyan Liu, Jine Yang, Swati Kannan, Andreas Burchert, Zdzislaw Szulc, Alicja Bielawska, Keiko Ozato, Kapil Bhalla, Kebin Liu
Journal: Cancer Research (2011)

Abstract IFN regulatory factor 8 (IRF8) is a key transcription factor for myeloid cell differentiation and its expression is frequently lost in hematopoietic cells of human myeloid leukemia patients. IRF8-deficient mice exhibit uncontrolled clonal expansion of undifferentiated myeloid cells that can progress to a fatal blast crisis, thereby resembling human chronic myelogeneous leukemia (CML). Therefore, IRF8 is a myeloid leukemia suppressor. Whereas the understanding of IRF8 function in CML has recently improved, the molecular mechanisms underlying IRF8 function in CML are still largely unknown. In this study, we identified acid ceramidase (A-CDase) as a general transcription target of IRF8. We demonstrated that IRF8 expression is regulated by IRF8 promoter DNA methylation in myeloid leukemia cells. Restoration of IRF8 expression repressed A-CDase expression, resulting in C16 ceramide accumulation and increased sensitivity of CML cells to FasL-induced apoptosis. In myeloid cells derived from IRF8-deficient mice, A-CDase protein level was dramatically increased. Furthermore, we demonstrated that IRF8 directly binds to the A-CDase promoter. At the functional level, inhibition of A-CDase activity, silencing A-CDase expression, or application of exogenous C16 ceramide sensitized CML cells to FasL-induced apoptosis, whereas overexpression of A-CDase decreased CML cells' sensitivity to FasL-induced apoptosis. Consequently, restoration of IRF8 expression suppressed CML development in vivo at least partially through a Fas-dependent mechanism. In summary, our findings determine the mechanism of IRF8 downregulation in CML cells and they determine a primary pathway of resistance to Fas-mediated apoptosis and disease progression. Cancer Res; 71(8); 2882–91. ©2011 AACR.
ON THE MODE OF ACTION OF SULFANILAMIDE IN EXPERIMENTAL STREPTOCOCCUS EMPYEMA
Authors: Frederick P. Gay, Ada R. Clark
Journal: The Journal of Experimental Medicine (1937)

Sulfanilamide prevents the evolution of an invariably fatal streptococcus empyema in rabbits when it is given repeatedly and in sufficient doses subcutaneously. Complete sterilization of the inoculated cavity occurs on approximately the 2nd day. The serum, defibrinated blood and artificial pleural exudate of similarly treated animals inhibits the growth of the same streptococcus in the test tube but even repeated doses of such treated blood serum fail to sterilize the culture. The coccal chains grown in such drugged serum are elongated and present pleomorphic and metachromatic organisms and may give rise to colonies that are at first less predominantly mucoid in appearance. Such organisms have, however, lost little if any of their virulence. Cooperation on the part of locally derived clasmatocytes is apparently required in complete sterilization of the animal body. This conclusion is reached not only by a process of exclusion from comparison with the test tube results, but through the direct histological demonstration of a precocious and increasing mobilization of clasmatocytes in the parietal and visceral pleura of treated animals. In other words, sulfanilamide apparently produces a bacteriostasis sufficiently marked to protect the accumulated leucocytes and to allow the natural defense macrophages to accumulate. There is direct evidence that the drug does not in itself stimulate the mobilization of the macrophages. There is no evidence that the cell reaction which finally accounts for disposal of the organisms is other than local.
Chemical inhibitors of phagosome-lysosome fusion in cultured macrophages also inhibit saltatory lysosomal movements. A combined microscopic and computer study.
Authors: P D Hart, M R Young, M M Jordan, W J Perkins, M J Geisow
Journal: The Journal of Experimental Medicine (1983)

The effects on lysosomal movements produced by the weak base ammonium chloride and by a representative polyanion poly-D-glutamic acid (PGA), previously reported to inhibit phagosome-lysosome (P-L) fusion, have been studied in cultured mouse macrophages using direct visual phase-contrast microscopy, a previously described (1, 3, 7) fluorescence assay of fusion, and computer analysis techniques. Treatment of the macrophages with 5-10 mM NH4Cl for 0.5-2 h or with 100 micrograms PGA/ml for 5 d caused a striking inhibition of saltatory lysosomal movements, as well as the expected inhibition of P-L fusion. Two other anionic fusion inhibitors tested, dextran sulphate and suramin, inhibited movements similarly. Removal of the NH4Cl from the cell medium reversed the lysosomal stasis and restored P-L fusion. Computer analyses of changes in lysosomal positions in treated and untreated macrophages during 2, 10, and 30-s intervals, using data from photomicrographs, computer graphics, and quantitative nearest-neighbour techniques developed for this purpose, supported the qualitative visual observation of the inhibition of lysosomal movements by the fusion inhibitors NH4Cl and PGA. Over the chosen intervals, from 80 to 96% of the lysosomes could be paired within 1 micron of each other in the NH4Cl- and PGA-treated cells in comparison with 50-70% in normal cells. The differences between the drug-treated and normal cells were highly significant. In an analogous system, the lysosomal stasis induced by hypertonic sucrose was examined and it was observed that P-L fusion too was inhibited. Both effects were reversible. We conclude that inhibition of P-L fusion and of lysosomal movement are associated. We suggest a causal relationship between these changes, namely, that the lysosomotropic inhibitors of fusion under study produce their effects largely, though perhaps not exclusively, by reducing saltatory lysosomal motion and consequently periphagosomal assembly, rather than directly and independently on P-L contact or on the fusion process itself. The possibility is raised that microtubules may be involved in the effector mechanism of these modulations.
Evidence of Pre-Roman Tribal Genetic Structure in Basques from Uniparentally Inherited Markers
Authors: Begoña Martínez-Cruz, Christine Harmant, Daniel E. Platt, Wolfgang Haak, Jeremy Manry, Eva Ramos-Luis, David F. Soria-Hernanz, Frédéric Bauduer, Jasone Salaberria, Bernard Oyharçabal, Lluis Quintana-Murci, David Comas
Journal: Molecular Biology and Evolution (2012)

Basque people have received considerable attention from anthropologists, geneticists, and linguists during the last century due to the singularity of their language and to other cultural and biological characteristics. Despite the multidisciplinary efforts performed to address the questions of the origin, uniqueness, and heterogeneity of Basques, the genetic studies performed up to now have suffered from a weak study design where populations are not analyzed in an adequate geographic and population context. To address the former questions and to overcome these design limitations, we have analyzed the uniparentally inherited markers (Y chromosome and mitochondrial DNA) of ~900 individuals from 18 populations, including those where Basque is currently spoken and populations from adjacent regions where Basque might have been spoken in historical times. Our results indicate that Basque-speaking populations fall within the genetic Western European gene pool, that they are similar to geographically surrounding non-Basque populations, and also that their genetic uniqueness is based on a lower amount of external influences compared with other Iberians and French populations. Our data suggest that the genetic heterogeneity and structure observed in the Basque region result from pre-Roman tribal structure related to geography and might be linked to the increased complexity of emerging societies during the Bronze Age. The rough overlap of the pre-Roman tribe location and the current dialect limits support the notion that the environmental diversity in the region has played a recurrent role in cultural differentiation and ethnogenesis at different time periods.
THE INFLUENCE OF DIET ON IRON ABSORPTION
Authors: D. Mark Hegsted, Clement A. Finch, Thomas D. Kinney
Journal: The Journal of Experimental Medicine (1949)

Rats fed a corn grit diet containing large amounts of ferric citrate absorb and deposit excessive amounts of iron in their livers. Undoubtedly various factors are involved in iron absorption, but these studies indicate that the low level of dietary phosphate was primarily responsible. The addition of phosphate salts to this diet has shown that the amount of iron deposited in the liver was inversely related to the phosphorus content of the diet. It is possible to obtain excessive iron deposits in the livers of animals receiving a normal diet, by adding large amounts of iron salts to the diet. This is not associated with losses of body weight in these animals. It is concluded that the absolute amount of iron and/or phosphorus in the diet as well as the iron-phosphorus ratio influences the amount of iron absorbed.