tbuckley/cabot-search huggingface dataset:
Feedback Control Through cGMP-Dependent Protein Kinase Contributes to Differential Regulation and Compartmentation of cGMP in Rat Cardiac Myocytes
Authors: Liliana R.V. Castro, Julia Schittl, Rodolphe Fischmeister
Journal: Circulation Research (2010)

Rationale: We have shown recently that particulate (pGC) and soluble guanylyl (sGC) cyclases synthesize cGMP in different compartments in adult rat ventricular myocytes (ARVMs). Objective: We hypothesized that cGMP-dependent protein kinase (PKG) exerts a feedback control on cGMP concentration contributing to its intracellular compartmentation. Methods and Results: Global cGMP levels, cGMP-phosphodiesterase (PDE) and pGC enzymatic activities were determined in purified ARVMs. Subsarcolemmal cGMP signals were monitored in single cells by recording the cGMP-gated current ( I CNG ) in myocytes expressing the wild-type rat olfactory cyclic nucleotide-gated (CNG) channel. Whereas the NO donor S -nitroso- N -acetyl-penicillamine (SNAP) (100 μmol/L) produced little effect on I CNG , the response increased 2-fold in the presence of the PKG inhibitors KT5823 (50 nmol/L) or DT-2 (2 μmol/L). The effect of KT5823 was abolished in the presence of the nonselective cyclic nucleotide PDE inhibitor 3-isobutyl-1-methylxantine (IBMX) (100 μmol/L) or the selective cGMP-PDE5 inhibitor sildenafil (100 nmol/L). PKG inhibition also potentiated the effect of SNAP on global cGMP levels and fully blocked the increase in cGMP-PDE5 activity. In contrast, PKG inhibition decreased by ≈50% the I CNG response to ANP (10 and 100 nmol/L), even in the presence of IBMX. Conversely, PKG activation increased the I CNG response to ANP and amplified the stimulatory effect of ANP on pGC activity. Conclusions: PKG activation in adult cardiomyocytes limits the accumulation of cGMP induced by NO donors via PDE5 stimulation but increases that induced by natriuretic peptides. These findings support the paradigm that cGMP is not uniformly distributed in the cytosol and identifies PKG as a key component in this process.
Early effect of ultrarush venom immunotherapy on the IgG antibody response
Authors: A. Michils, S. Baldassarre, C. Ledent, M. Mairesse, B. Gossart, J. Duchateau
Journal: Allergy (2000)

Background: We have previously shown in several allergy models that allergic and tolerance status with respect to allergens is associated with a somewhat different dominant specificity of IgG antibodies. The objective was to test this hypothesis in the compelling model of ultrarush venom immunotherapy (VIT), which induces clinical tolerance after only a few hours of treatment. Methods: Antibody titers and specificity were evaluated through solid‐phase ELISA using streptavidin‐biotin technology in 12 patients allergic to wasp venom before and during the ultrarush procedure (at 12 h, 24 h, and 15 days). The results were compared with those from another group of 20 patients treated with venom injections for at least 2 years. Results: No significant change was observed in IgG titers during the early phase of VIT. The capacity of individual sera to prevent the antigen binding of pooled IgG from allergic patients changed rapidly, with mean percentage inhibitions falling from 80±15%, before starting VIT, to 26±14%, 35±15%, and 34±5% after 12 h, 24 h, and 15 days of treatment, respectively ( P &lt;0.001 by one‐way ANOVA). The capacity of individual sera to prevent the antigen binding of pooled IgG from patients receiving prolonged VIT changed, with mean percent inhibitions increasing from 47±8%, before starting VIT, to 76±7%, 83±6%, and 87±6% after 12 h, 24 h, and 15 days of treatment, respectively ( P &lt;0.001 by one‐way ANOVA). Conclusions: During the initial phase of ultrarush VIT, a change in IgG specificity, i.e., a change in the set of epitopes dominantly recognized by IgG on wasp‐venom antigens, occurred concomitantly with early clinical tolerance and was already detectable a few hours after the onset of treatment. Although it may be an epiphenomenon, this change represents the earliest humoral modification described so far during this procedure. The mechanism is unknown, but it appears to be a selective depletion of the highest avidity antibody fraction by the venom injected in large doses at this stage of therapy. Finally, our data now show the previously documented association between a particular IgG specificity and the clinical status (allergy vs tolerance) to be true also with ultrarush VIT, a model in which the clinical ability to display allergic symptoms is rapidly reversed.
Evidence for the generation of hydroxyl radical during arachidonic acid metabolism by human platelets
Authors: Daljeet Singh, James E. Greenwald, Joseph Bianchine, Earl N. Metz, Arthur L. Sagone
Journal: American Journal of Hematology (1981)

Abstract Reactive oxygen species, probably hydroxyl radicals (OH·), have been suggested to be generated during arachidonic acid (AA) metabolism and, once released, these species can modify the rate and extent of various reactions involved in AA metabolism. We have studied this phenomenon in washed human platelets. OH· generation was quantitated using 14 C‐benzoic acid as a specific trap in a continuous ionization chamber system. Resting platelets did not produce any detectable signal, whereas addition of AA resulted in gradual OH· production with peak values detected at approximately 20 min. Similar studies conducted under nitrogen or after boiling the platelets almost abolished OH· generation. Aspirin had no significant effect, whereas 5,8,11,14‐eicosatetraynoic acid decreased the signal by &gt; 90%, thus suggesting that OH· is produced primarily through the lipoxygenase pathway. Superoxide dismutase (SOD) and catalase had no effect and, as expected, phenol and mannitol decreased OH· production considerably, by &gt; 50% and 90%, respectively. Azide and cyanide also reduced the OH· generation by about two‐thirds. We conclude that OH· is generated during AA metabolism by human platelets. It is primarily produced via the lipoxygenase pathway and may require a heme‐dependent peroxidase. This highly reactive oxidant may play an important role in normal and abnormal hemostasis.
Epithelioid blue naevus of the genital mucosa: report of four cases.
Authors: M.J. Izquierdo, M.A. Pastor, L. Carrasco, C. Moreno, H. Kutzner, O.P. Sangueza, L. Requena
Journal: British Journal of Dermatology (2001)

Epithelioid blue naevi are an unusual cytological variant of blue naevus that have been recently described mostly in patients with the Carney complex, although they may also occur in isolation. This variant of blue naevus is composed of melanin-laden polygonal epithelioid melanocytes situated within the dermis. The neoplastic cells show no maturation with progressive depth of dermal infiltration and, in contrast with the usual stromal changes in blue naevi, epithelioid blue naevi exhibit no dermal fibrosis. We describe four cases of epithelioid blue naevus located on the genital mucosa in four patients with no evidence of the Carney complex. Three male patients showed an epithelioid blue naevus on the mucosa of the glans penis and a female patient had a lesion of the right labium minoris. Histopathologically, the lesions consisted of entirely intradermal melanocytic naevi composed mostly of heavily pigmented epithelioid melanocytes involving the dermis of the genital mucosa. Immunohistochemically, in all cases, epithelioid melanocytes expressed immunoreactivity for S-100 protein, HMB-45, Melan-A and MiTF antibodies.
Improve chest compressions to reduce deaths from cardiac arrest, new guidance says
Authors: S. Mayor
Journal: BMJ (2010)

People untrained in resuscitation should be encouraged to perform chest compressions but not to give rescue breaths to people with cardiac arrest, recommend new UK guidelines.

The guidelines emphasise the importance of maintaining continuous chest compressions in a person with cardiac arrest, as interruptions commonly occur and are associated with a reduced chance of survival. Compressions are often not deep enough—whether carried out by healthcare professionals in hospital or by others outside­­—and at too slow a rate.

Less than 10% of people who have cardiac arrests outside hospital survive to be discharged after subsequent hospital treatment. Research indicates that this …
DNR or PEACE?
Authors: John Crampton
Journal: BMJ (2008)

I have huge difficulty in discussing “do not resuscitate” (DNR) orders with people whose loved ones are close to death, especially if this is untimely, unexpected, or non-malignant. This remains the case even when we know cardiopulmonary intervention would be futile. The response “But, doctor, surely we should give him a chance?” is all too frequent, and the explanation that the patient has no chance sounds arrogant, unhelpful, …
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS
Authors: K. Landsteiner, M. W. Chase
Journal: The Journal of Experimental Medicine (1939)

Experiments are described on the latency period in sensitization to poison ivy and on the time necessary for the agent to remain in contact with the skin. The chief matter of investigation concerned the manner in which the whole skin becomes sensitive following treatment at a particular site, and especially whether this is effected by way of the epidermis. Two methods were used to interrupt the continuity of the skin, one by cutting through both skin and the underlying thin muscular layer, the other by removing a strip of skin so as to spare the skin muscle. These procedures led to different results when poison ivy extract was applied to the areas thus isolated. In the first case, sensitization was mostly prevented, whereas with the second method generalized hypersensitiveness occurred almost uniformly. An explanation is to be found in the severance of the lymph vessels lying on the surface of the muscular layer, pointing to the necessity of a free lymph passage. On the other hand the experiments prove that general sensitization is not dependent upon maintaining the integrity of the skin around a treated area. An inhibition of sensitization by incisions extending through the panniculus carnosus was seen to some extent in anaphylactic sensitization with protein antigens, namely when sufficiently small amounts were employed.
Colonic lesion histology prediction: comparison between experts, registrars, consultants, BCS nurses and endoscopy research fellows
Authors: P. J. Basford, R. J. Mead, T. Uraoka, T. Matsuda, P. Bhandari
Journal: Gut (2011)

<h3>Introduction</h3> Studies of in vivo diagnosis have shown accuracy of 68–83% using conventional white light endoscopy and up to 94–96% with chromoendoscopy/zoom endoscopy in expert hands. Specific training in lesion recognition, use of advanced imaging techniques and chromoendoscopy is not widespread amongst UK trainees. We aimed to assess the competence of UK registrars9 and consultants9 polyp recognition skills plus the impact of a dedicated lesion recognition intervention. <h3>Methods</h3> We developed a library of paired endoscopic pictures of 37 lesions (15 adenomas, 13 hyperplastic and 9 cancers) with and without dye spray. In a previous study using the same image library Japanese and UK expert endoscopists demonstrated histology prediction accuracy of 92% and 87%, respectively. Subjects were classified into 4 groups; Consultants (n = 5), Gastroenterology Registrars (n = 8) and Endoscopy Research Fellows (n = 3). Bowel Cancer Screening Nurse Practitioners (BCSN, n = 4) with no previous training in polyp recognition were used as controls. All subjects aside from the BCSN group were performing colonoscopy on a regular basis. Endoscopy Research Fellows had received specific training in lesion recognition using Kudo9s pit patterns, Paris Classification and a novel polyp classification system (NAC) described previously. <h3>Results</h3> Mean accuracy scores compared to histology were BCSN 59%, Registrar 62.7%, Consultant 69.0% and Fellows 82%. The mean accuracy score for Fellows was significantly higher than each of the other three groups (p &lt; 0.05 for all 3 comparisons). There was no significant difference in accuracy between the BCSN and Registrar groups (p = 0.139). Consultants had significantly higher accuracy scores than Registrars (p &lt; 0.05). Senior gastroenterology registrars (Year 4 or above) were not significantly more accurate than more junior registrars (Year 1–3) (63.5% vs 62.0%, p = 0.612). Similarly, there was no difference in accuracy between those registrars who had achieved JAG independence in colonoscopy, and those who had not (63.4% vs 62.3%, p = 0.751). Zoom chromoendoscopy reduced accuracy in all doctor groups (70.6% WL vs 63.4% Zoom), but increased accuracy in BCSN (51.3% WL vs 63.5% Zoom). <h3>Conclusion</h3> High accuracy in lesions recognition can be achieved in expert hands. Greater experience and independence in colonoscopy do not appear to increase accuracy in lesion recognition amongst registrars. Zoom endoscopy is intended to improve lesion recognition skills but our results suggest a paradoxical effect suggesting a lack of familiarity with this modality. Dedicated training improves lesion recognition skills amongst registrars. This calls for a dedicated lesion recognition skills programme for all colonoscopists.
Indomethacin normalizes intracranial pressure in acute liver failure: A twenty-three-year-old woman treated with indomethacin
Authors: J O Clemmesen, B A Hansen, F S Larsen
Journal: Hepatology (1997)

In patients with acute liver failure, cerebral herniation is a common cause of death. The present study reports the effect of indomethacin on four occasions of intracranial hypertension, in a 23-year old previously healthy woman with severe acetaminophen poisoning. During each episode of intracranial hypertension, the patient was treated with 25 mg of indomethacin, and each time the intracranial pressure normalized. We recommend further controlled studies to determine the exact effect of indomethacin on cerebral blood flow and metabolism before it is recommended for treatment of intracranial hypertension in patients with acute liver failure.
Allergy To Betalactams In Brazil: Placebo Effect Or Misdiagnosis?
Authors: Manoela Crespo-Magalhães, Marcelo Vivolo Aun, Roberta Almeida-Castro, Marisa Rosimeire Ribeiro, Laila Sabino Sabino Garro, Jorge Kalil, Antonio Abílio Motta, Pedro Giavina-Bianchi
Journal: Journal of Allergy and Clinical Immunology (2014)
Improving the selection of medical students
Authors: D. Powis
Journal: BMJ (2010)

Non-academic personal qualities should be taken into account

In a study reported in this issue (doi:10.1136/bmj.c478), James and colleagues assess whether a new test, the UK Clinical Aptitude Test (UKCAT), improves the selection process for school leaver applicants to medical (and dental) schools 1.

Doctors, of whatever specialty calling, need specialist medical knowledge and a complementary palette of skills and personality traits if they are to be professionally competent. Regardless of the specialty—surgeon or psychiatrist, general practitioner or pathologist—most would agree on what basic skills and traits doctors should have; conversely on what traits, attitudes, and behaviours that they should not possess. Any competency list for a generic medical practitioner should comprise excellent academic ability, good cognitive skills, and the ability to use academic knowledge appropriately in quantitative, verbal, and spatial domains. Practitioners should also have well developed decision making skills, professional integrity, highly developed moral standards, and excellent interpersonal skills, in addition to being accomplished and confident communicators who can empathise with patients. They must be able to function professionally when under stress, have a good measure of self control, and not be prone to taking inappropriate risks in a practice setting. Their mental …
EFFECTS OF CILOSTAZOL ON THE CANINE RV WEDGE MODEL OF BRUGADA SYNDROME
Authors: Rong Bai, Han-Xuan Tan, Rong-Hui Yu, Lei Ruan, Yang Liu, Nian Liu, Yan-Fei Ruan, Jian-Zeng Dong, Chang-Sheng Ma
Journal: Journal of the American College of Cardiology (2014)
Increased Resistance of Mycobacterium Tuberculosis to Drug Therapy
Authors: Enrique Gerszten
Journal: JAMA (1963)

Four hundred eighty-two Negro tuberculous patients were followed after the admission sensitivity tests of their organisms to high levels of streptomycin, isoniazid, and para-aminosalicylic acid was known. They were classified on the basis of their histories as new or old patients, depending on whether or not they had had prior therapy; 44% of the new patients and 67% of the old patients had organisms resistant to one or more of the three antituberculous agents used. The patient's rate of recovery decreased as the resistance of his organisms increased. Patients with prior therapy developed chronic disease or died of their tuberculosis 3 1/2 times more frequently than patients without prior therapy.
Treatment of disseminated granuloma annulare with a 5-lipoxygenase inhibitor and vitamin E
Authors: K.J. Smith, C. Norwood, H. Skelton
Journal: British Journal of Dermatology (2002)

Journal Article Treatment of disseminated granuloma annulare with a 5‐lipoxygenase inhibitor and vitamin E Get access K.J. Smith, K.J. Smith Departments of Dermatology and Kathleen J.Smith. E‐mail: hskelton@path.uab.edu Search for other works by this author on: Oxford Academic Google Scholar C. Norwood, C. Norwood Department of Dermatology, National Naval Medical Center, Bethesda, MD, U.S.A Search for other works by this author on: Oxford Academic Google Scholar H. Skelton H. Skelton Pathology, University of Alabama, Eye Foundation Hospital, Suite 414, 1720 University Blvd, Birmingham, AL 35294‐0009, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 4, 1 April 2002, Pages 667–670, https://doi.org/10.1046/j.1365-2133.2002.04590.x Published: 01 April 2002 Article history Accepted: 12 September 2001 Published: 01 April 2002
Bhagwan Dayal Shrivastava
Authors: S E Shrivastava
Journal: BMJ (2002)

Senior hospital medical officer in ophthalmology Boston Combined Hospitals and Pilgrim Hospital, Boston, Lincolnshire, 1963-88 (b India 1929; q Agra 1952), d 17 September 2002.

In the 1970s Shriv, or Dr Shriv as he was known by his patients, was British national champion in petanque or “boules,” as it is commonly called in France. He represented Great Britain in the world championships held in Luxembourg. He was president of the British Petanque Association in the 1980s and also a national and international umpire. He leaves a wife, Susan; and two children.
Syngamus in an Australian.
Authors: B A Latham
Journal: BMJ (1978)

cook to boil an egg, but it is hardly necessary or desirable.Doctors should be important teachers of health care and be able to concentrate their other skills and expertise mainly on complex problems and diseases which are often their major interest.This would ensure the greater availability of appropriate care at all the required levels for people who might otherwise be denied this.Many may feel threatened by change and resist any delegation of part of their traditional roles.Innovative schemes with all acting in a responsible fashion should ensure both the greater wellbeing of the community and justifiably earn the trust of patients.The primary health care nurse is a valuable member of the health care team in her own right and should not be seen as a "doctor-substitute" or assistant.
Characterization of TRPC2, an Essential Genetic Component of VNS Chemoreception, Provides Insights into the Evolution of Pheromonal Olfaction in Secondary-Adapted Marine Mammals
Authors: Li Yu, Wei Jin, Jia-xin Wang, Xin Zhang, Meng-meng Chen, Zhou-hai Zhu, Hang Lee, Muyeong Lee, Ya-ping Zhang
Journal: Molecular Biology and Evolution (2010)

Pheromones are chemical cues released and sensed by individuals of the same species, which are of major importance in regulating reproductive and social behaviors of mammals. Generally, they are detected by the vomeronasal system (VNS). Here, we first investigated and compared an essential genetic component of vomeronasal chemoreception, that is, TRPC2 gene, of four marine mammals varying the degree of aquatic specialization and related terrestrial species in order to provide insights into the evolution of pheromonal olfaction in the mammalian transition from land to water. Our results based on sequence characterizations and evolutionary analyses, for the first time, show the evidence for the ancestral impairment of vomeronasal pheromone signal transduction pathway in fully aquatic cetaceans, supporting a reduced or absent dependence on olfaction as a result of the complete adaptation to the marine habitat, whereas the amphibious California sea lion was found to have a putatively functional TRPC2 gene, which is still under strong selective pressures, reflecting the reliance of terrestrial environment on chemical recognition among the semiadapted marine mammals. Interestingly, our study found that, unlike that of the California sea lion, TRPC2 genes of the harbor seal and the river otter, both of which are also semiaquatic, are pseudogenes. Our data suggest that other unknown selective pressures or sensory modalities might have promoted the independent absence of a functional VNS in these two species. In this respect, the evolution of pheromonal olfaction in marine mammals appears to be more complex and confusing than has been previously thought. Our study makes a useful contribution to the current understanding of the evolution of pheromone perception of mammals in response to selective pressures from an aquatic environment.