tbuckley/cabot-search huggingface dataset:
Abstract 16018: Impaired Intrinsic Myocardial Shortening in Both Two Directions and Compensatory Mechanism to Maintain Left Ventricular Ejection Fraction in Patients With Hypertensive Heart Disease
Authors: Satoshi Yamada, Kazunori Okada, Hisao Nishino, Hiroyuki Iwano, Daisuke Murai, Taichi Hayashi, Masahiro Nakabachi, Ayako Ichikawa, Shinobu Yokoyama, Sanae Kaga, Taisei Mikami, Hiroyuki Tsutsui
Journal: Circulation (2014)

Background: Longitudinal myocardial shortening is known to be reduced even if left ventricular (LV) ejection fraction (EF) is preserved in patients with hypertensive heart disease (HHD). However, the compensatory mechanism remains to be elucidated. Thus layer-specific longitudinal and circumferential strain as well as stress-strain relationship was observed in HHD patients. Methods: In 46 HHD patients with preserved EF (&gt;50%) and 29 age-matched control subjects, global longitudinal strain (LS) and layer-specific circumferential strain (CS) were measured from the apical 4-chamber view and mid-ventricular short-axis view, respectively, by using speckle tracking echocardiography. LS was measured at innermost LV wall layer, and CS at innermost, midwall, and outermost layers. Layer-specific end-systolic circumferential wall stress (CWS) according to Mirsky’s formula and endocardial meridional wall stress (MWS) were calculated. Results: Systolic blood pressure (147±20 mm Hg), interventricular septal thickness (13±2 mm), and LV dimension (48±4 mm) were greater in HHD than controls, whereas EF was comparable (66±8 vs 66±5%). LS was smaller in HHD than controls (-13±3 vs -17±3%, p&lt;0.001) in spite of reduced MWS (520±141 vs 637±164 dyn·mm -2 , p&lt;0.01), suggesting impaired longitudinal myocardial function in HHD. Similarly, CS was smaller in HHD than controls at outer layer (-6.8±2.2 vs -8.8±2.2%, p&lt;0.01) and at midwall (-11.3±3.4 vs -13.9±3.2%, p&lt;0.01) in spite of reduced CWS (outer: 238±82 vs 336±110 dyn·mm -2 , p&lt;0.001; mid: 360±107 vs 473±131 dyn·mm -2 , p&lt;0.001). In contrast, at the innermost layer, both CS (-26±5 vs -25±5%, p=0.41) and CWS (979±153 vs 992±139 dyn·mm -2 , p=0.72) were comparable between groups. Furthermore, the difference of CS between inner and outer layers significantly correlated with relative wall thickness (r=-0.33, p&lt;0.01). Finally, CS at inner layer significantly correlated with EF (r=-0.43, p&lt;0.001), whereas LS did not. Conclusions: In patients with HHD, intrinsic myocardial shortening was impaired both longitudinally and circumferentially. Some compensatory mechanism associated with increased relative wall thickness might work to maintain subendocardial CS, resulting in preserved EF.
Association of Predeployment Heart Rate Variability With Risk of Postdeployment Posttraumatic Stress Disorder in Active-Duty Marines
Authors: Arpi Minassian, Adam X. Maihofer, Dewleen G. Baker, Caroline M. Nievergelt, Mark A. Geyer, Victoria B. Risbrough
Journal: JAMA Psychiatry (2015)

<h3>Importance</h3> Disrupted autonomic nervous system functioning as measured by heart rate variability (HRV) has been associated with posttraumatic stress disorder (PTSD). It is not clear, however, whether reduced HRV before trauma exposure contributes to the risk for development of PTSD. <h3>Objective</h3> To examine whether HRV before combat deployment is associated with increased risk of a PTSD diagnosis after deployment when accounting for deployment-related combat exposure. <h3>Design, Setting, and Participants</h3> Between July 14, 2008, and May 24, 2012, active-duty Marines were assessed 1 to 2 months before a combat deployment and again 4 to 6 months after their return. The first phase of the Marine Resiliency Study (MRS-I) included 1415 male Marines, 59 of whom developed PTSD after deployment. Participants in the second phase of the Marine Resiliency Study (MRS-II) included 745 male Marines, 25 of whom developed PTSD after deployment. Analysis was conducted from November 25, 2013, to April 16, 2015. <h3>Main Outcomes and Measures</h3> Predeployment HRV was measured via finger photoplethysmography during a 5-minute period of rest. Frequency-domain measures of HRV were generated. Diagnosis of PTSD was determined using the Clinician-Administered PTSD Scale. <h3>Results</h3> After accounting for deployment-related combat exposure, lower HRV before deployment as measured by an increased low-frequency (LF) to high-frequency (HF) ratio of HRV was associated with risk of PTSD diagnosis after deployment (combined MRS-I and MRS-II cohort meta-analysis odds ratio, 1.47; 95% CI, 1.10-1.98;<i>P</i> = .01). The prevalence of postdeployment PTSD was higher in participants with high predeployment LF:HF ratios (15.8% [6 of 38 participants]) compared with participants who did not have high LF:HF ratios (3.7% [78 of 2122 participants]). <h3>Conclusions and Relevance</h3> This prospective longitudinal study provides initial and modest evidence that an altered state of autonomic nervous system functioning contributes to PTSD vulnerability, taking into account other key risk factors. If these findings are replicated, interventions that change autonomic nervous system function may open novel opportunities for prevention and treatment of PTSD.
INSECTS AND WAR: XIII.--THE MOSQUITO (Anophcles maculipennis)
Authors: A. E. Shipley
Journal: BMJ (1915)

The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that reside in the endoplasmic reticulum membranes and that undergo post-translational modifications (PTMs). UGT2B7 is of particular interest because of its action on a wide variety of drugs. Most studies currently survey common variants and examine only a small fraction of the genetic diversity; however, rare variants (frequency &lt;1%) might have a significant effect because they are predicted to greatly outnumber common variants in the human genome. We discovered a rare single nucleotide <i>UGT2B7</i> variant of potential pharmacogenetic relevance that encodes a nonconservative amino acid substitution at codon 121. This low-frequency variation, found in two individuals of a population of 305 healthy volunteers, leads to the translation of an asparagine instead of an aspartic acid (UGT2B7 p.D<sup>121</sup>N). This amino acid change was predicted to create a putative N-glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H treatment of microsomal fractions and inhibition of N-glycosylation of endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293) cells. The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely affecting proper protein folding, resulted in a significant decrease of 49% and 40% in the formation of zidovudine and mycophenolic acid glucuronides, respectively. A systematic survey of the Short Genetic Variations database uncovered 32 rare, naturally occurring missense variations predicted to create or disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. Collectively, these variants have the potential to increase the proportion of variance explained in the UGT pathway resulting from changes in PTMs, such as N-linked glycosylation with consequences on drug metabolism.
Undifferentiated pleomorphic sarcoma in a child with type 1 neurofibromatosis
Authors: R.R. Patel, S. Meehan, S.J. Orlow
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, A 10‐year‐old girl without significant past medical history presented with a slightly tender scalp nodule, growing for several months. On examination, there was a 1·5 cm rubbery, mobile, subcutaneous nodule on the left parieto‐occipital scalp. Additionally, she had axillary and inguinal freckling, seven large café‐au‐lait macules (CALMs) ranging in size from 1 to 6·5 cm, and numerous small CALMs less than 1 cm in size. Neurofibromas were not present, and there were no obvious bony abnormalities. Her family history was unremarkable, and she had had a reportedly normal ophthalmological examination at age 6 years. An excision of the scalp lesion was performed. On examination, there was a fragmented, firm tumour with a yellow‐white surface and focal haemorrhage. On cross‐section, the cut surface had a ‘fish flesh‐like’ appearance. Microscopic examination revealed a proliferation of two populations of cells. The first was organized predominantly as storiform fascicles and comprised of cells with plump, spindle‐shaped, hyperchromatic nuclei, and the second was arranged as sheets of cells with enlarged hyperchromatic and pleomorphic nuclei. There were also numerous multinucleated cells, some of which were osteoclast‐like (Figs 1a and 2a). Mitotic figures, some atypical, were readily observed (Fig. 2b). Immunoperoxidase studies revealed that the atypical cells reacted for CD68 (Fig. 1b) but were not reactive for smooth muscle actin, desmin, AE1/AE3, EAB 903 or S100 protein. Following wide local excision, the patient remains disease free to date.
Brief Communication: Inhibition of Migration of Murine Spleen Cells by Rauscher Leukemia Virus-Infected Syngeneic Cells
Authors: Peter J. Fimmel, Kerry O. Cox, David Keast
Journal: JNCI Journal of the National Cancer Institute (1975)

The in vitro migration of spleen cells from BALB/c mice infected with Rauscher leukemia virus (RLV) was markedly inhibited 10 days after RLV inoculation. Mixtures of infected and uninfected spleen cells used in the ratio of 1:4 in an effector-cell/indicator-cell system showed that viable RLV-infected spleen cells could inhibit the migration of uninfected spleen cells in a manner indistinguishable from that mediated by sensitized spleen cell reacting to specific antigen.
540. Retroviral Mediated Gene Transfer of Hexb in Sandhoff Disease
Authors: Xiaohan Du, Li Xu, Wenge Zhang, Susan Tang, NayWei Soong, Michael B. Zwick, Dennis R. Burton, Robert G. Whalen
Journal: Molecular Therapy (2004)

Top of pageAbstract
Vaccines that stimulate broadly neutralizing antibodies to HIV-1 will have a major impact on reducing transmission. However this remains an elusive goal because the antibodies induced by the envelope glycoprotein (Env) do not effectively neutralize primary isolates or viral strains that are important in transmission. Using DNA shuffling and screening technologies, we had identified novel gp120 variants with preferential reactivity to the neutralizing human mAb b12 and significantly weakened binding to non-neutralizing CD4BS-binding mAbs b3 and b6. This phenotype mimics that of the native trimeric envelope complex. Biacore studies of mAb-gp120 interaction demonstrated that the enhanced affinity of b12 in the shuffled variants resulted largely from a decrease in the dissociation rate. DNA shuffling of the 'core' form of gp120, which lacks V1/V2, V3 and parts of C1 and C5, also generated gp120 variants that possessed these antigenic properties.

We immunized rabbits with >100 independent gp120 variants using electroporation-mediated DNA vaccination, followed by boosting with a heterologous or homologous recombinant protein antigen. A single-cycle pseudovirus-based assay was used to evaluate the HIV-1 neutralization activities of purified immunoglobulins. About 60% of the full-length gp120 variants induced neutralizing antibodies to the TCLA strain SF162, indicating that the DNA shuffling and screening approach provides novel variants that have gp120-like immunogenicity. Several of the shuffled variants induced antibodies to primary viral isolates and five clones were able to neutralize eight primary isolates in addition to TCLA strains. These shuffled variants are candidates for additional shuffling to screen for further improvements in immunogenicity and for testing using additional vaccine formats, including optimized immunization protocols.

DNA shuffling extensively recombines mixtures of parental genes such as the Env coding sequences to create highly functional libraries of shuffled chimeras. We have successfully applied this technology to evolve novel viral phenotypes, to improve the antigenicity of the Hepatitis B virus envelope protein and to generate tetravalent Dengue virus antigens. The application of DNA shuffling to HIV vaccine development provides a new approach for generating novel Env structures as vaccine candidates.
Expanding the Boundaries of Health and Social Science: Case Studies in Interdisciplinary Innovation
Authors: A. D. Spiegel
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Clinical Characteristics and Treatment Outcomes of Autoimmune‐Associated Hemophagocytic Syndrome in Adults
Authors: Shunichi Kumakura, Yohko Murakawa
Journal: Arthritis & Rheumatology (2014)

To better define the clinical characteristics and treatment outcomes of autoimmune-associated hemophagocytic syndrome (AAHS) in adults.Adults with AAHS (defined as pathologic evidence of hemophagocytosis without any obvious cause other than an autoimmune disease) were identified through a review of the literature.Among 116 patients identified, underlying diseases included systemic lupus erythematosus (SLE) in 52.3%, adult-onset Still's disease (AOSD) in 26.7%, and dermatomyositis in 6.9%. Fever, lymphadenopathy, hepatomegaly, and splenomegaly were found in 86.8%, 41.0%, 41.8%, and 45.5% of patients, respectively. Cytopenia, liver dysfunction, and hyperferritinemia developed frequently, and coagulopathy was seen in 50.6% of patients. Normal or low C-reactive protein levels were characteristic of patients with underlying SLE. The most commonly used therapy was corticosteroids, which were initially administered in 95.7% of patients, with 57.7% responding. Patients with corticosteroid-refractory disease were usually treated with cyclosporine, intravenous cyclophosphamide (IV CYC), or intravenous immunoglobulin (IVIG), with IV CYC being highly effective. Treatment with biologic agents resulted in favorable effects in the majority of patients. The mortality rate was 12.9%. Male sex (odds ratio [OR] 6.47, 95% confidence interval [95% CI] 2.06-30.39, P < 0.01), dermatomyositis (OR 5.57, 95% CI 1.08-28.65, P < 0.05), and anemia (hemoglobin <8 gm/dl; OR 3.74, 95% CI 1.02-13.8, P < 0.05) were identified as factors associated with mortality.AAHS is potentially fatal. Corticosteroids are a mainstay of initial treatment. For corticosteroid-refractory disease, IV CYC may be beneficial as compared with cyclosporine or IVIG. Treatment that proceeds directly from corticosteroids to biologic agents is promising.
US scientists develop a possible test for BSE
Authors: Scott Gottlieb
Journal: BMJ (1999)

A group of US agricultural scientists have developed a laboratory assay that might lead to the creation of a cheap diagnostic blood test for transmissible spongiform encephalopathies, including bovine spongiform encephalopathy.

The test, developed by private and government researchers working at the US Agricultural Research Service in Ames, Iowa, detects the presence of abnormal proteins called prions that cause transmissible spongiform encephalopathies.

The human form of bovine spongiform encephalitis, variant Creutzfeldt-Jakob (vCJD), is the best known of the group and has affected about …
Allergic disorders in African countries: linking immunology to accurate phenotype
Authors: R. Van Ree, M. Yazdanbakhsh
Journal: Allergy (2007)

Identification and characterization of risk and protective factors for allergy is important for developing strategies for prevention or treatment. The prevalence of allergy is clearly higher in affluent countries than in developing countries like, e.g. Africa. Especially in urban areas of developing countries, allergy is however on the increase. In Africa, we have the unique opportunity to investigate risk and protective factors and the influence of urbanization and westernization, i.e. almost to take a look at Europe, Australia or the USA as they were before their allergy epidemics. Moreover, migrants from developing to affluent countries experiencing an increased burden of allergy provide new insights into risk and protective factors. Allergen exposure, diet and infections are the major exogenous influences playing a role as risk and protective factors. Depending on the nature, timing, chronicity and level of exposure, each of them can promote or inhibit allergy. Perhaps with the exception of infections, availability of data from Africa on their role in the development of allergy is limited. Detailed epidemiological studies in rural and urban Africa combined with basic immunological research are needed to unravel mechanisms of increase in allergy and of protection. The maturation of the immune system at young age under influence of exogenous factors results in differences in T‐cell‐skewing (Th1/Th2/Treg) and humoral responses. It is essential to perform studies from a ‘non‐Eurocentric’ angle (e.g. local allergens, locally validated questionnaires and diagnostic procedures). Such studies will provide the affluent countries with new leads to combat the allergy epidemic and more importantly help prevent it in Africa.
A memorable patient: All in a day's work
Authors: E. R Nye
Journal: BMJ (2000)

At 82 she was still a beautiful woman. Her numerous medical problems and her elbow crutch did not diminish her elegance and her speech, polished by some high class English boarding school for girls as well as the years spent being the gracious hostess at colonial garden parties.

I gradually got round to the reason for her seeing me for a cardiological opinion. Chest pain? …
Behavior &lt;italic&gt;In Vitro&lt;/italic&gt; of a Mouse Lymphoid-Leukemia Virus&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Robert A. Manaker, Patsy C. Strother, Alice A. Miller, Chester V. Piczak
Journal: JNCI Journal of the National Cancer Institute (1960)

Maintenance of the Moloney murine leukemia virus in serial passage in vitro has been established. With the techniques for culture described, replication of the agent occurred in cultures of normal mouse spleen without evidence of gross cytopathic changes. The induction of leukemia in mice served to demonstrate the infectivity of tissue-culture fluids. Infected cultures continued to produce virus for extended periods without subculture. When there was an interval of 2 or more weeks between passages in normal mouse-spleen cultures, the leukemia agent could be propagated in continuous passage in vitro.
Lack of association between Chlamydia pneumoniaeseropositivity and aortic atherosclerotic plaques
Authors: Yoram Agmon, Bijoy K Khandheria, Irene Meissner, Tanya M Petterson, W.Michael O’Fallon, Teresa J.H Christianson, David O Wiebers, Thomas F Smith, James M Steckelberg, A.Jamil Tajik
Journal: Journal of the American College of Cardiology (2003)
Prognostic Implications of Restrictive Left Ventricular Filling in Acute Myocardial Infarction: A Serial Doppler Echocardiographic Study 11To discuss this article on-line, visit the ACC Home Page at www.acc.org/membersand click on the JACC Forum
Authors: Francisca Nijland, Otto Kamp, Aart J.P Karreman, Machiel J van Eenige, Cees A Visser
Journal: Journal of the American College of Cardiology (1997)
Abstract 17570: Rescue of Dilated Cardiomyopathy in Nav1.5 Mutant Mice Defective in Calmodulin Binding by Inhibition of Late Na+ Current
Authors: Hana Cho, Takeshi Aiba, Deborah DiSilvestre, Victoria Halperin, Eiki Takimoto, Rajesh Sekar, Leslie Tung, Gordon F Tomaselli
Journal: Circulation (2014)

Introduction: Nav1.5, the main voltage-gated Na+ channel in the heart, has been shown to be involved in many cardiac diseases such as long QT syndrome, Brugada syndrome, and heart failure. Na+ channels are importantly regulated by Ca2+ calmodulin (CaM) mediated signaling: however, a fundamental understanding and physiological significance of CaM regulation of Na+ channel is incomplete. Here, we have created a transgenic mouse that harbors a mutated CaM binding motif (NaV1.5-IQ/AA), which is critical for Na+ channel regulation by Ca2+-CaM. Methods: Ventricle mass and function were analyzed with electrocardiogram, echocardiogram, and detailed invasive pressure-volume analysis. Additionally, single ventricular myocytes were obtained. Whole cell patch clamp was used to record membrane ionic currents, including sodium current, Ca2+ current, K+ currents and NCX current. Results: Homozygous mice are embryonic lethal and IQ/AA+/- mice exhibit a dramatic phenotype consisting of dilated cardiomyopathy (DCM) at 4-6 months of age with prolongation of QT. The Na+ current in IQ mice exhibits an enhanced slowly inactivating late component (INa,L) with concomitant up regulation of Na+/Ca2+ exchanger currents. Consistent with other models of DCM and heart failure, DCM in IQ/AA+/- mice was associated with a down regulation of transient outward K+ currents (Ito) and an increase in T-type Ca2+ currents. Chronic treatment with ranolazine designed to block INa,L prevented electrical remodeling of the hearts including an increase in INa,L and a down regulation of Ito. Consistent with the changes in INa,L and Ito, in ranolazine-fed IQ/AA+/- mice, the QT interval was decreased compared to vehicle (p&lt;0.05). Further, the contractile dysfunction, cardiac hypertrophy, and myocardial fibrosis were attenuated in all ranolazine- fed animals, while ventricular dysfunction persisted in animals not fed drug (p&lt;0.05). Conclusions: The data suggest that loss of CaM-mediated regulation of Na+ channel induces dilated cardiomyopathy by enhancing late Na+ current. Taken together, our data demonstrate a dynamic interplay for Ca2+ and Na+ signaling via the CaM binding motif of Na+ channels and highlight the critical importance of late Na+ currents to myopathy and arrhythmia.
A memorable patient: Keep looking for a reason
Authors: M. Powell
Journal: BMJ (2000)

Sarah was 22 when she presented with the dreadful signs of a large space-occupying lesion deep in the dominant parietal lobe. She was drowsy with a severe headache, had severe dysphasia, and there was a significant rightsided weakness. The computed tomography said it all;a malignant intrinsic tumour at the trigone of the lateral ventricle, probably a glioblastoma.

She rallied a little on steroids overnight and so I performed a craniotomy, having suitably warned her worried family of the likely outcome and prognosis. I found a very bloody tumour that had some definition from the surrounding brain. The pathologist told me that the frozen section showed a highly malignant brain tumour, consistent with the radiologist's diagnosis.

The survival from this type of tumour in this position is measured in months, and …