tbuckley/cabot-search huggingface dataset:
A baby with noisy breathing
Authors: J. Thuerey, D. S. Urquhart, G. Wilkinson
Journal: BMJ (2010)

A 13 week old boy presented to accident and emergency with fever, breathing difficulties, and reduced feeding. On examination, his respiratory rate was 60 breaths/min, pulse was 180 beats/min, oxygen saturation was 91% in air, and temperature was 37.8ºC. He had intercostal and subcostal recession and a tracheal tug. Auscultation of the chest showed widespread wheeze and crackles and heart sounds were normal. A chest radiograph showed an obscured right heart border and generalised hyperinflation. Blood tests showed a white cell count of 22.0×109/l, and a nasopharyngeal aspirate was positive for respiratory syncytial virus on polymerase chain reaction testing. The boy was born at term by normal delivery with a birth weight of 4100 g. The antenatal course was uneventful. He was kept in hospital for two days after delivery because he was “mucousy.” His parents described him as a noisy and “snuffly” breather since birth, with frequent coughing and “choking” episodes. Because of this he had been seen by his general practitioner and in casualty several times, but he had not been admitted to hospital before. He had been breast fed and was thriving well. A few hours after admission he suddenly deteriorated after a feed. His pulse rose to 230 beats/min and respiratory rate to 80 breaths/min. Capillary gas showed pH 7.03, partial pressure of carbon dioxide 12.18 kPa, bicarbonate 17 mmol/l, and base excess −7.4. He was admitted to paediatric intensive care and was intubated and ventilated. He remained intubated for 10 days and two attempts to extubate failed because he developed stridor. Once extubated successfully, we performed further investigations to check for any underlying abnormality. The following radiological image was obtained (fig 1⇓).
Rebreathing in a subject wearing an integral crash helmet.
Authors: R Greenbaum, A F Malins, R Davies, P J Baskett
Journal: BMJ (1982)

The respired air of a volunteer was analysed while he was wearing a variety of integral crash helmets. Observations were made with and without a protective balaclava, bib or scarf, or both. Rebreathing occurred and the peak inspired oxygen tension fell as low as 16.0 kPa (120 mm Hg) with a minimum inspired carbon dioxide of 2.1 KPa (16.0 mm Hg). Accessories worn or attached to the helmet which restrict airflow into the helmet should not be used. Attention should be paid to the "air conditioning" of helmets when worn with flameproof balaclavas and bibs.
The Sebright Bantam Chicken and the Genetic Control of Extraglandular Aromatase*
Authors: JEAN D. WILSON, MARK LESHIN, FREDRICK W. GEORGE
Journal: Endocrine Reviews (1987)

NO ASPECT of sexual dimorphism is more striking or more variable among species than is the feathering pattern of birds. One such sexual difference involves the morphology of feathers. For example, in some birds the feathers of the male are longer and more deeply fringed than those of the female.1 Species in which such sexual differences are extreme include the lyre bird, the peacock, some types of hummingbird, and the domestic chicken (1). Owing to their accessibility, chickens have been the favored subjects for the study of relationships between gonadal function and feather structure, and it is customary to characterize the plumage of adult chickens as either henny or cocky (Fig. 1) (3). In the hen most feathers are short and straight and have a solid vane with many barbules and hence little fringing. In the rooster, in contrast, the neck hackle feathers, the feathers of the saddle (the median tail coverts), and the major tail coverts and great sickle feathers of the tail are long and deeply fringed owing to the paucity of barbules on the distal ends of the feather barbs.
PEEP and low tidal volume ventilation reduce lung water in porcine pulmonary edema.
Authors: M Colmenero-Ruiz, E Fernández-Mondéjar, M A Fernández-Sacristán, R Rivera-Fernández, G Vazquez-Mata
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

This study analyzed the effect of both positive end-expiratory pressure (PEEP) and reduction in tidal volume (VT) on extravascular lung water (EVLW) in a permeability model of pulmonary edema. Immediately after producing a pulmonary edema with oleic acid, 21 pigs were randomized into three groups. Group I (n = 8): PEEP of 0 cm H2O (ZEEP), VT of 12 ml/kg; Group II (n = 6): PEEP of 10 cm H2O, VT of 12 ml/kg; Group III (n = 7): PEEP of 10 cm H2O, VT of 6 ml/kg. EVLW was measured by the double indicator method (DI) at baseline (time 0) and after 30, 60, 120, 180, and 240 min and by the gravimetric method (G) at 240 min. Both methods correlated excellently (r = 0.94, p < 0.0001). EVLW-DI was significantly less with PEEP application (Group II versus Group I) at 180 min and thereafter. Likewise, EVLW-DI was less throughout the experimental period with reduced VT once PEEP was applied (Group III versus Group II). EVLW-G was less in Group II than in Group I at 16.3 +/- 2.7 and 23.2 +/- 4.2 ml/kg, respectively (p < 0.0001), and less in Group III than in Group II at 10.7 +/- 0.9 and 16.3 +/- 2.7 ml/kg (p < 0.0001). We conclude that early application of 10 cm H2O of PEEP reduces EVLW in permeability pulmonary edema. The lowering of VT reduced EVLW even further.
Rheumatoid Nodules and Rheumatoid Granulomas in Systemic Lupus Erythematosus
Authors: Edmund L. Dubois
Journal: JAMA (1972)

Rheumatoid granulomas may occur in classic systemic lupus erythematosus (SLE) as either an early or late manifestation of the disease. Nine patients had biopsy-proven granulomas, six in subcutaneous nodules of the elbow, two in synovial tissue, and one in the wall of a giant dissecting synovial cyst. Three patients had chronic deforming nonerosive polyarthritis characterized by extensive destruction of capsular tissues, ulnar deviation, and subluxation deformity of the postrheumatic fever or Jaccoud type. Rheumatoid granulomas were found in the synovium of the metacarpophalangeal joint in two of them and in a giant dissecting synovial cyst of the elbow in one. The occurrence of rheumatoid granulomas in both SLE and rheumatoid arthritis emphasizes the close association of the two disorders and that rheumatoid granulomas in adults are not unique to rheumatoid arthritis.
Calcium release microdomains and mitochondria
Authors: Michael Kohlhaas, Christoph Maack
Journal: Cardiovascular Research (2013)

The processes of excitation–contraction (EC) coupling consume large amounts of energy that need to be replenished by oxidative phosphorylation in the mitochondria. Since Ca2+ activates key enzymes of the Krebs cycle in the mitochondrial matrix, it is important to understand the mechanisms and kinetics of mitochondrial Ca2+ uptake to delineate how in cardiac myocytes, energy supply is efficiently matched to demand. In recent years, the identification of various proteins involved in mitochondrial Ca2+ signalling and the tethering of mitochondria to the sarcoplasmic reticulum (SR) has considerably advanced the field and supported the concept of a mitochondrial Ca2+ microdomain, in which Ca2+ concentrations are high enough to overcome the low Ca2+ affinity of the principal mitochondrial Ca2+ uptake mechanism, the Ca2+ uniporter. Furthermore, defects in EC coupling that occur in heart failure disrupt SR-mitochondrial Ca2+ crosstalk and may cause energetic deficit and oxidative stress, both factors that are thought to be causally involved in the initiation and progression of the disease.
High quality, low cost healthcare can be provided in US, experts say
Authors: J. H. Tanne
Journal: BMJ (2012)

The frontal mechanisms of motor intention were studied in dorsal premotor and motor cortex of monkeys making direct reaches to visual targets and online corrections of hand trajectory, whenever a change of the target9s location occurred. This study and our previous one of parietal cortex (Archambault et al., 2009) provide a picture on the evolution of motor intention and online control of movement in the parietofrontal system. In frontal cortex, significant relationships were found between neural activity and hand kinematics (position, speed, and movement direction). When a change of motor intention occurred, the activity typical of the movement to the first target smoothly evolved into that associated with the movement toward the second one, as observed during direct reaches. Under these conditions, parietal cells remained a more accurate predictor of hand trajectory than frontal ones. The time lags of neural activity with hand kinematics showed that motor, premotor, and parietal cortex were activated sequentially. After the first target9s presentation and its change of location, the population activity signaled the change of motor plan before the hand moved to the initial target9s position. This signaling occurred earlier in premotor than in motor and parietal cortex. Thus, premotor cortex encodes a higher-order command for the correction of motor intention, while parietal cortex seems responsible for estimating the kinematics of the motor periphery, an essential step to allow motor cortex to modify the hand trajectory. This indicates that the parietofrontal system can update an original and not-yet-accomplished motor plan during its execution.
Hypoxia predisposes neonatal rat ventricular myocytes to apoptosis induced by activation of the Fas (CD95/Apo-1) receptor: Fas activation and apoptosis in hypoxic myocytes
Authors: G. Yaniv, M. Shilkrut, R. Lotan, G. Berke, S. Larisch, O. Binah
Journal: Cardiovascular Research (2002)

Objective: Since apoptosis is an important contributor to heart diseases in which ischemia and hypoxia are key elements, we tested the hypothesis that hypoxia predisposes neonatal rat ventricular myocytes (NRVM) to Fas-mediated apoptosis, by shifting the balance between antiapoptotic and proapoptotic proteins towards the latter. Methods: Normoxic or hypoxic (22 h, 1% O2) cultured NRVM were exposed to recombinant Fas L (rFasL) for 7 h, and apoptosis measured thereafter. Results: Whereas in normoxic NRVM, rFasL did not cause apoptosis measured by the TUNEL assay (4.8±0.5% in control versus 4.5±0.9% in rFasL), in hypoxic cultures rFasL increased the background apoptosis level by 100%. That Fas was functional in normoxic NRVM, despite its inability to mediate apoptosis, was evidenced by the finding that Fas activation increased the diastolic [Ca2+]i levels measured by Fura 2 fluorescence, and caused arrhythmias. In support of our working hypothesis, hypoxia increased Fas expression by 200% (measured by quantitative Western blot), and the expression of the proapoptotic proteins ARTS and FADD by 323 and 250%, respectively, and decreased the expression of the antiapoptotic proteins ARC and FLIP by 90 and 60%, respectively. Conclusion: By upregulating Fas expression and key proapoptotic proteins, and by downregulating antiapoptotic proteins, hypoxia predisposes ventricular myocytes to Fas-induced apoptosis.
Dementia in the Presenium
Authors: Frank J. Ayd
Journal: JAMA (1974)

Few physicians are cognizant of the magnitude of the problem generated by the presenile dementias. There are more than 30,000 victims of this disorder in the United States and they occupy about one fourth of the total mental hospital beds. These conditions often occur in men and women at a time when they are most powerful in human affairs. If unrecognized and untreated, these dementias can have deleterious consequences not only for the patient but for society as a whole. The authors decided to write this book "because there is no practical synopsis which orders and describes the presenile dementias that could serve as a guide to their recognition and facilitate early effective treatment when available." Their objective was to fill this void at least partially and they have succeeded. In a lucid, easily comprehended exposition, they provide experienced clinicians and students a concise historical review of the evolution of
Molecular regulation of hepatocellular transport systems in cholestasis
Authors: Michael Trauner, Peter J. Meier, James L. Boyer
Journal: Journal of Hepatology (1999)

Cholestasis is an impairment of bile secretion which may result either from a functional defect in bile formation at the level of the hepatocytes (hepatocellular cholestasis) or from an impairment in bile secretion and flow at the level of bile ductules or ducts (ductular/ductal cholestasis) (1). The hepatic uptake and biliary excretion of bile salts and a number of other organic anions is mediated by specific transport proteins in hepatocytes. Studies of the molecular alterations of hepatocellular membrane transporters in experimental models and clinical cholestatic disorders are leading to a rapid increase in knowledge in this field. Evidence now exists that decreased or even absent expression of hepatocellular transport systems may explain impaired transport function resulting in hyperbilirubinemia and cholestasis. This review summarizes the molecular alterations of hepatocellular membrane transporters in clinical and experimental forms of cholestatic liver disease.
William Tod Thom
Authors: Charles Court-Brown
Journal: BMJ (2006)

​FormerFormer principal medical officer Edinburgh (b 1917; q Edinburgh 1940; OBE, FFCM, FFPHM), died from heart failure on 20 April 2006.



Figure 1



Bill's war service was mainly spent in Africa and India, and after demobilisation he joined the Colonial Service and returned to Africa. He worked as a medical officer in Tanganyika, Somaliland, and latterly in Sarawak. On his return to the United Kingdom in 1964 he worked as a medical officer in Birmingham before moving back to Scotland in 1966. Bill was concerned with the medical aspects of services for elderly people and undertook pioneering work in exposing the appalling conditions in many long-stay hospitals in Scotland. He leaves a wife, Betty; two children; and three grandchildren.
Psychosocial Conferences in Medical Oncology
Authors: ARTHUR I. RICHARDS
Journal: Annals of Internal Medicine (1974)

Training programs in medical oncology should provide formal psychosocial education. The program at the Strong Memorial Hospital, Rochester, New York, includes biweekly conferences attended by members of the Medical Oncology and the Medical-Psychiatric Liaison staffs. These sessions are concerned with specific patient-oriented problems. Several examples of such conferences are described, including their applicability to the overall management of the patient.
THE DIFFERENTIATION AND ABERRATIONS OF SEX CHARACTERISTICS
Authors: W. Blair-Bell
Journal: BMJ (1935)

t Hermaplhroditos-the son of Hermes (the messenger of the Gods) and Aphrodite (Venus)-was so beloved by the nymph of the well Salmacis that she begged the Gods to unite them for ever.The Gods answered her prayer very literally.The result was no doubt quoted by the ancient Greeks as a typical example of the divine origin of pathological conditions.Hippocrates, commenting on this belief, expresses his agreement in a general way, but in his scientific wisdom ad(Is: " Each condition has its natural principle, and none exists without its natural cause."to-day.Naturally, before the microscope came into use there could be no recognition of the nuclear processes which lead to cell division, of which we now have some information in relation to the mechanism of sex differentia-
Dendritic Cells in Tumor-Associated Tertiary Lymphoid Structures Signal a Th1 Cytotoxic Immune Contexture and License the Positive Prognostic Value of Infiltrating CD8+ T Cells
Authors: Jérémy Goc, Claire Germain, Thi Kim Duy Vo-Bourgais, Audrey Lupo, Christophe Klein, Samantha Knockaert, Luc de Chaisemartin, Hanane Ouakrim, Etienne Becht, Marco Alifano, Pierre Validire, Romain Remark, Scott A. Hammond, Isabelle Cremer, Diane Damotte, Wolf-Herman Fridman, Catherine Sautès-Fridman, Marie-Caroline Dieu-Nosjean
Journal: Cancer Research (2013)

Tumor-infiltrating T cells, particularly CD45RO(+)CD8(+) memory T cells, confer a positive prognostic value in human cancers. However, the mechanisms that promote a protective T-cell response in the tumor microenvironment remain unclear. In chronic inflammatory settings such as the tumor microenvironment, lymphoid neogenesis can occur to create local lymph node-like structures known as tertiary lymphoid structures (TLS). These structures can exacerbate a local immune response, such that TLS formation in tumors may help promote an efficacious immune contexture. However, the role of TLS in tumors has yet to be investigated carefully. In lung tumors, mature dendritic cells (DC) present in tumor-associated TLS can provide a specific marker of these structures. In this study, we evaluated the influence of TLS on the characteristics of the immune infiltrate in cohorts of prospective and retrospective human primary lung tumors (n = 458). We found that a high density of mature DC correlated closely to a strong infiltration of T cells that are predominantly of the effector-memory phenotype. Moreover, mature DC density correlated with expression of genes related to T-cell activation, T-helper 1 (Th1) phenotype, and cytotoxic orientation. Lastly, a high density of TLS-associated DC correlated with long-term survival, which also allowed a distinction of patients with high CD8(+) T-cell infiltration but a high risk of death. Taken together, our results show how tumors infiltrated by TLS-associated mature DC generate a specific immune contexture characterized by a strong Th1 and cytotoxic orientation that confers the lowest risk of death. Furthermore, our findings highlight the pivotal function of TLS in shaping the immune character of the tumor microenvironment, in promoting a protective immune response mediated by T cells against cancer.
Cell-permeable Peptide Tat-PSD-95 PDZ2 Inhibits Chronic Inflammatory Pain Behaviors in Mice
Authors: Feng Tao, Qingning Su, Roger A. Johns
Journal: Molecular Therapy (2008)

Inflammatory conditions can lead to persistent debilitating pain, and the activation of N-methyl-D-aspartate receptors (NMDARs) has been shown to play an important role in the processing of inflammatory pain. Postsynaptic density protein-95 (PSD-95), a scaffolding protein, has been identified to interact with NMDARs at neuronal synapses of the central nervous system (CNS). However, the role of these interactions in the central sensitization of nociceptive processing has not been defined. In this study, we investigated the effect of disrupting NMDAR/PSD-95 interactions on chronic inflammatory pain behaviors. We constructed a fusion peptide, Tat-PSD-95 PDZ2, comprising the second PDZ domain of PSD-95, to disrupt specifically NMDARs/PSD-95 protein interactions. Western blot analysis showed that Tat-PSD-95 PDZ2 intraperitoneally injected into mice was delivered intracellularly into neurons in the CNS. By in vitro and in vivo binding assays, we found that the Tat-PSD-95 PDZ2 dose dependently inhibited the interactions between NMDARs and PSD-95. Furthermore, behavioral testing showed that mice given Tat-PSD-95 PDZ2 exhibited significantly reduced complete Freund's adjuvant (CFA)-induced chronic inflammatory pain behaviors compared to the vehicle-treated group. Our results indicate that by disrupting NMDAR/PSD-95 protein interactions, the cell-permeable fusion peptide Tat-PSD-95 PDZ2 provides a new target and approach for chronic inflammatory pain therapy. Inflammatory conditions can lead to persistent debilitating pain, and the activation of N-methyl-D-aspartate receptors (NMDARs) has been shown to play an important role in the processing of inflammatory pain. Postsynaptic density protein-95 (PSD-95), a scaffolding protein, has been identified to interact with NMDARs at neuronal synapses of the central nervous system (CNS). However, the role of these interactions in the central sensitization of nociceptive processing has not been defined. In this study, we investigated the effect of disrupting NMDAR/PSD-95 interactions on chronic inflammatory pain behaviors. We constructed a fusion peptide, Tat-PSD-95 PDZ2, comprising the second PDZ domain of PSD-95, to disrupt specifically NMDARs/PSD-95 protein interactions. Western blot analysis showed that Tat-PSD-95 PDZ2 intraperitoneally injected into mice was delivered intracellularly into neurons in the CNS. By in vitro and in vivo binding assays, we found that the Tat-PSD-95 PDZ2 dose dependently inhibited the interactions between NMDARs and PSD-95. Furthermore, behavioral testing showed that mice given Tat-PSD-95 PDZ2 exhibited significantly reduced complete Freund's adjuvant (CFA)-induced chronic inflammatory pain behaviors compared to the vehicle-treated group. Our results indicate that by disrupting NMDAR/PSD-95 protein interactions, the cell-permeable fusion peptide Tat-PSD-95 PDZ2 provides a new target and approach for chronic inflammatory pain therapy.
Nutrient-Content Claims — Guidance or Cause for Confusion?
Authors: Allison C. Sylvetsky, William H. Dietz
Journal: New England Journal of Medicine (2014)

The FDA is considering changes to its Nutrition Facts label, but other labeling changes would help consumers select nutritious foods. One key concern is sugar- and calorie-related claims, especially with regard to nonnutritive sweeteners and product sweetness.
Combination Therapy with Solifenacin and Tamsulosin Oral Controlled Absorption System in a Single Tablet for Lower Urinary Tract Symptoms in Men: Efficacy and Safety Results from the Randomised Controlled NEPTUNE Trial
Authors: Philip van Kerrebroeck, Christopher Chapple, Ted Drogendijk, Monique Klaver, Roman Sokol, Mark Speakman, Klaudia Traudtner, Marcus J. Drake
Journal: European Urology (2013)
Abstract 3350: CIP2A regulates cell proliferation via akt signaling pathway in human lung cancer
Authors: Ningjing Lei, Bo Peng, Jiangying Zhang
Journal: Cancer Research (2014)

Abstract CIP2A is an intracellular endogenous protein phosphatase 2A (PP2A) inhibitor with oncogenic activities. CIP2A was initially identified as a tumor-associated antigen (TAA) in gastric and liver cancer patients, and it was overexpressed in a variety of cancer types. Recently, we found that CIP2A was overexpressed in human lung cancer specimens as compared to normal lung tissues. The elevated expression of CIP2A in lung cancer cells results in an increased cell proliferation. The observation on the association between CIP2A and AKT phosphorylation at S473 in our lab and other labs suggested the role of CIP2A in regulating AKT phosphorylation. Our preliminary data indicated that CIP2A might promote cell proliferation through AKT signaling pathway under growth factor stimulation. Interestingly, the depletion of CIP2A in lung cancer cells did not induce a global change of AKT phosphatase activity, which implied that CIP2A might recognize specific AKT targets and play certain roles in the signaling pathway. In this study, we identified several AKT substrates specifically targeted by CIP2A, such as Hsp70 and mTOR, by proteomic-based systematic screening. The candidates obtained from our study will expand the understanding on protein-substrate interaction and therefore direct the cancer drug design. Therefore, our study addressed a novel role of CIP2A in mediating cancer progression through interacting with AKT pathway in a substrate-dependent manner. Citation Format: Ningjing Lei, Bo Peng, Jiangying Zhang. CIP2A regulates cell proliferation via akt signaling pathway in human lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3350. doi:10.1158/1538-7445.AM2014-3350