tbuckley/cabot-search huggingface dataset:
Exosome-mediated Delivery of the Intrinsic C-terminus Domain of PTEN Protects It From Proteasomal Degradation and Ablates Tumorigenesis
Authors: Syed Feroj Ahmed, Nilanjana Das, Moumita Sarkar, Uttara Chatterjee, Sandip Chatterjee, Mrinal Kanti Ghosh
Journal: Molecular Therapy (2014)

PTEN mutation is a frequent feature across a plethora of human cancers, the hot-spot being its C-terminus (PTEN-CT) regulatory domain resulting in a much diminished protein expression. In this study, the presence of C-terminus mutations was confirmed through sequencing of different human tumor samples. The kinase CKII-mediated phosphorylation of PTEN at these sites makes it a loopy structure competing with the E3 ligases for binding to its lipid anchoring C2 domain. Accordingly, it was found that PTEN-CT expressing stable cell lines could inhibit tumorigenesis in syngenic breast tumor models. Therefore, we designed a novel exosome-mediated delivery of the intrinsic PTEN domain, PTEN-CT into different cancer cells and observed reduced proliferation, migration, and colony forming ability. The delivery of exosome containing PTEN-CT to breast tumor mice model was found to result in significant regression in tumor size with the tumor sections showing increased apoptosis. Here, we also report for the first time an active PTEN when its C2 domain is bound by PTEN-CT, probably rendering its anti-tumorigenic activities through the protein phosphatase activity. Therefore, therapeutic interventions that focus on PTEN E3 ligase inhibition through exosome-mediated PTEN-CT delivery can be a probable route in treating cancers with low PTEN expression. PTEN mutation is a frequent feature across a plethora of human cancers, the hot-spot being its C-terminus (PTEN-CT) regulatory domain resulting in a much diminished protein expression. In this study, the presence of C-terminus mutations was confirmed through sequencing of different human tumor samples. The kinase CKII-mediated phosphorylation of PTEN at these sites makes it a loopy structure competing with the E3 ligases for binding to its lipid anchoring C2 domain. Accordingly, it was found that PTEN-CT expressing stable cell lines could inhibit tumorigenesis in syngenic breast tumor models. Therefore, we designed a novel exosome-mediated delivery of the intrinsic PTEN domain, PTEN-CT into different cancer cells and observed reduced proliferation, migration, and colony forming ability. The delivery of exosome containing PTEN-CT to breast tumor mice model was found to result in significant regression in tumor size with the tumor sections showing increased apoptosis. Here, we also report for the first time an active PTEN when its C2 domain is bound by PTEN-CT, probably rendering its anti-tumorigenic activities through the protein phosphatase activity. Therefore, therapeutic interventions that focus on PTEN E3 ligase inhibition through exosome-mediated PTEN-CT delivery can be a probable route in treating cancers with low PTEN expression.
Effect of various treatments on toxicity of inhaled vinylidene chloride.
Authors: R D Short, J M Winston, J L Minor, J Seifter, C C Lee
Journal: Environmental Health Perspectives (1977)

The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various treatments to alter parameters of toxicity was evaluated. Mice were more sensitive than rats both to the acute lethal and hepatotoxic effects of VDC. Disulfiram treatment reduced the acute lethal and hepatotoxic effects of inhaled VDC and reduced the levels of covalent bound radioactivity in the liver and kidney after the intraperitoneal administration of 14C-VDC. Treatment with diethyldithiocarbamate and thiram also protected mice from the acute lethal effects of VDC.
1125 A BAYESIAN MIXED TREATMENT COMPARISON EVALUATING THE RELATIVE EFFICACY OF CURRENTLY LICENSED HCV PROTEASE INHIBITORS FOR THE TREATMENT OF HCV GENOTYPE 1 INFECTION
Authors: J. Kieran, S. Schmitz, A. O'Leary, C. Bergin, S. Noms, C. Walsh, M. Barry
Journal: Journal of Hepatology (2012)
Hadzic’s Peripheral Nerve Blocks and Anatomy for Ultrasound-Guided Regional Anesthesia
Authors: Anthony Edelman
Journal: JAMA (2012)

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
Development and Validation of a Plasma Biomarker Panel for Discerning Clinical Significance of Indeterminate Pulmonary Nodules
Authors: Shaun Daly, Daniel Rinewalt, Cristina Fhied, Sanjib Basu, Brett Mahon, Michael J. Liptay, Edward Hong, Gary Chmielewski, Mark A. Yoder, Palmi N. Shah, Eric S. Edell, Fabien Maldonado, Aaron O. Bungum, Jeffrey A. Borgia
Journal: Journal of Thoracic Oncology (2012)
The history of osteoarthritis-osteoarthrosis
Authors: J Dequeker, F P Luyten
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background</h3> Idiopathic REM (rapid eye movement) sleep behaviour disorder (iRBD) has been implicated in cognitive impairments, but there is little evidence about progression of cognitive dysfunction in iRBD. <h3>Methods</h3> A retrospective follow-up study with patients with iRBD was performed. Conversion to neurodegenerative disorders was analysed by Kaplan-Meier survival analysis. Neuropsychological test results at baseline were compared between patients with iRBD and healthy controls. 57 patients with iRBD were successfully followed up for changes of cognitive performance over time (follow-up duration 50.84±25.38 months; range 12–108 months). Factors affecting cognitive decline were evaluated with multiple regression analysis and the subgroup analysis for groups with and without conversion was carried out. <h3>Results</h3> Among 84 patients with iRBD, conversion occurred in 18 patients and conversion rates were estimated to be 9%, 18% and 35% at 3, 5 and 6 years from diagnosis of iRBD. Individuals with iRBD showed lower z-scores at baseline than controls in Mini-Mental Status Examination, Trail Making Test A, constructional praxis and Executive Clock Drawing Task (CLOX2). Patients with non-converting iRBD showed significant performance decline in memory (p=0.003, Digit span forward) and a worsening tendency of executive functions (p=0.007, frontal assessment battery; p=0.012, Stroop test) at follow-up tests. Cognitive decline was associated with disease duration or follow-up duration, and lower executive function at baseline increased conversion risk (p=0.031). <h3>Conclusions</h3> Patients with iRBD have cognitive impairments at baseline and progressive cognitive decline over time. Even in idiopathic cases without development of any neurodegenerative disease, degenerative changes in cognition seem to be under way.
Small Cell Carcinoma of the Urinary Bladder Treated with Chemotherapy and Radiotherapy: Results in Five Cases
Authors: R. Bast&uacute;s, J.M. Caballero, G. Gonz&aacute;lez, P. Borrat, J. Casalots, G. Gomez de Segura, Ll. Mart&iacute;, J. Ristol, L. Cirera
Journal: European Urology (1999)
The key role of peptidoglycan in the opsonization of Staphylococcus aureus.
Authors: P K Peterson, B J Wilkinson, Y Kim, D Schmeling, S D Douglas, P G Quie, J Verhoef
Journal: Journal of Clinical Investigation (1978)

In an effort to determine the staphylococcal cell surface component(s) of importance in opsonization, cell walls (peptidoglycan and teichoic acid) and peptidoglycan were isolated from Staphylococcus aureus strain H grown in [3H]glycine-containing broth. After incubation of the cell walls and peptidoglycan with various opsonic sources, uptake by human polymorphonuclear leukocytes was measured. The opsonic requirements for phagocytosis of cell walls and peptidoglycan were found to be similar to those of intact bacteria. Removal of teichoic acid from the cell wall did not affect opsonization. Likewise, a teichoic acid-deficient mutant strain of S. aureus H was opsonized in a manner similar to that of the parent strain. Immunoglobulin G functioned as the major heat-stable opsonic factor and both the classical and alternative pathways participated in opsonization. Kinetic studies revealed that opsonization of peptidoglycan, as well as C3-C9 consumption by peptidoglycan, proceeded at a slower rate via the alternative pathway (C2-deficient serum) than when the classical pathway was present (normal serum). The ability of peptidoglycan to activate C3-C9 was significantly reduced when normal and C2-deficient sera were preabsorbed with peptidoglycan at 2 degrees C suggesting that antibodies to peptidoglycan may be involved in activation of both the classical and alternative complement pathways. Thus, peptidoglycan appears to be the key cell wall component involved in staphylococcal opsonization, and it is suggested that host response to peptidoglycan, a major cell wall component of most gram-positive bacteria, may be related to the development of "natural immunity" to this group of microorganisms.
Outbreak of Influenza B in a Children's Home
Authors: Hugh L. Moffet, Henry G. Cramblett, Gordon K. Middleton, Joyce P. Black, Helen K. Shulenberger, Ann M. Yongue
Journal: JAMA (1962)

During a 20-day period in January, 1962, 133 of 280 normal children in a children's home were hospitalized with influenza, and detailed clinical and laboratory observations were made. The diagnosis was confirmed by isolation of Type B influenza virus or demonstration of a 4-fold hemagglutination-inhibiting antibody rise in 123 children. The majority of the children who were admitted had fever, headache, cough, and no localizing signs. Complications included pneumonia (3 cases), otitis media (4), and sinusitis (3 ). A 4-fold rise in<i>hemagglutination-inhibiting</i>antibody was demonstrated in 60% of the asymptomatic children who were not hospitalized. Influenza virus was recovered from the rectal swabbings of 11 of 96 children, a new observation which indicates that myxoviruses may be present in the feces more frequently than previously recognized.
Epigenetic silencing of the kinase tumor suppressor WNK2 is tumor-type and tumor-grade specific
Authors: Peter Jun, Chibo Hong, Anita Lal, Judith M. Wong, Michael W. McDermott, Andrew W. Bollen, Christoph Plass, William A. Held, Dominic J. Smiraglia, Joseph F. Costello
Journal: Neuro-Oncology (2008)

Both genetic and epigenetic mechanisms contribute to meningioma development by altering gene expression and protein function. To determine the relative contribution of each mechanism to meningioma development, we used an integrative approach measuring copy number and DNA methylation changes genomewide. We found that genetic alterations affected 1.9%, 7.4%, and 13.3% of the 691 loci studied, whereas epigenetic mechanisms affected 5.4%, 9.9%, and 10.3% of these loci in grade I, II, and III meningiomas, respectively. Genetic and epigenetic mechanisms rarely involved the same locus in any given tumor. The predilection for epigenetic rather than genetic silencing was exemplified at the 5′ CpG island of WNK2, a serine-threonine kinase gene on chromosome 9q22.31. WNK2 is known to negatively regulate epidermal growth factor receptor signaling via inhibition of MEK1 (mitogen-activated protein kinase kinase 1), and point mutations have been reported in WNK1, WNK2, WNK3, and WNK4. In meningiomas, WNK2 was aberrantly methylated in 83% and 71% of grade II and III meningiomas, respectively, but rarely in a total of 209 tumors from 13 other tumor types. Aberrant methylation of the CpG island was associated with decreased expression in primary tumors. WNK2 could be reactivated with a methylation inhibitor in IOMM-Lee, a meningioma cell line with a densely methylated WNK2 CpG island and lack of WNK2 expression. Expression of exogenous WNK2 inhibited colony formation, implicating it as a potential cell growth suppressor. These findings indicate that epigenetic mechanisms are common across meningiomas of all grades and that for specific genes such as WNK2, epigenetic alteration may be the dominant, grade-specific mechanism of gene inactivation.
Psychosis after cannabis abuse.
Authors: M W Carney, L Bacelle, B Robinson
Journal: BMJ (1984)

of 90-100 mm Hg was visited two to three times weekly by the community midwife, who examined the patient's abdomen, tested urine, and measured blood pressure at each visit.After the 32nd week of pregnancy she viewed the patient's fetal movement chart.She was empowered to refer a patient back to the doctor at any time or straight to hospital if the diastolic blood pressure was greater than 100 mm Hg or she considered admission to be appropriate for any reason.If admission proved necessary the patient remained in hospital while the diastolic blood pressure was over 100 mm Hg, or if there was evidence of fetal compromise, and was then discharged home for further supervision.This policy was not implemented in women with accompanying proteinuria or suspected placental dysfunction.The table shows the results and compares them with the figures for the corresponding six months of 1982 when this policy was not in operation.No baby died or suffered morbidity as a result of the new policy.Admissions for hypertensive disease were significantly reduced when expressed as a proportion of all admissions (35/189 (18 5%) in 1982 v 19/173 (11°,) in 1983 (p<0-05)) and as a proportion of admissions initiated by medical staff (35/71 (49o`) v 19/166 (29°%) (p<0.02)).Altogether 112 inpatient bed days were saved over six months.Supervising hypertension associated with pregnancy added only 5%, to the workload of the community midwives, who welcomed the rewarding and responsible nature of the work.In ad- dition, a close personal relationship was established between patient and community midwife, which was of great benefit after delivery.Results of new policy of treatment for pregnant women with hypertension, 1983
Cytokine-Mediated Apoptosis in Cardiac Myocytes
Authors: Margaret A. Arstall, Douglas B. Sawyer, Ryuji Fukazawa, Ralph A. Kelly
Journal: Circulation Research (1999)

Abstract —Increased production of nitric oxide (NO) after induction of the cytokine-inducible isoform of nitric oxide synthase (iNOS or NOS2) in cardiac myocytes and other parenchymal cells within the heart may in addition to contributing to myocyte contractile dysfunction also contribute to the induction of programmed cell death (apoptosis). To investigate the mechanism(s) by which increased NO production leads to apoptosis, we examined the role of NO in primary cultures of neonatal rat ventricular myocytes (NRVMs) after induction by the cytokines interleukin-1β (IL-1β) and interferon γ (IFNγ) or exposure to the exogenous NO donor S -nitroso- N -acetylcysteine (SNAC) or peroxynitrite (ONOO − ). Both SNAC (1 mmol/L) and ONOO − (100 μmol/L), but not their respective controls (ie, N -acetylcysteine and pH-inactivated ONOO − ), induced apoptosis in confluent, serum-starved NRVMs at 48 hours. Similarly, incubation of NRVMs with IL-1β and IFNγ for 48 hours resulted in an increase in iNOS expression, nitrite production, and programmed cell death. Both the cytokine-induced nitrite accumulation and myocyte apoptosis could be completely prevented by the nonselective NOS inhibitor l -nitroarginine (3 mmol/L) or the specific iNOS inhibitor 2-amino-5,6-dihydro-6-methyl-4 H -1,3-thiazine (AMT, 100 μmol/L). NO-mediated myocyte apoptosis was not attenuated by the inhibition of soluble guanylyl cyclase with ODQ, nor could apoptosis be induced by the incubation of NRVMs with 1 mmol/L 8-bromo-cGMP, a cell-permeant cGMP analogue. However, NO-mediated apoptosis was significantly attenuated by the superoxide dismutase mimetic and ONOO − scavenger Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP, 100 μmol/L). NO/ONOO − -mediated apoptosis was associated with increased expression of Bax with no change in Bcl-2 mRNA abundance. Furthermore, apoptotic cell death was also confirmed in adult rat ventricular myocytes (ARVMs) when grown in heteroculture with IL-1β– and IFNγ-treated rat cardiac microvascular endothelial cells. Therefore, cytokine-induced apoptosis in NRVMs and ARVMs is mediated by iNOS induction, ONOO − , and associated with an increase in Bax levels.
Exacerbated Transplant Arteriosclerosis in Inducible Nitric Oxide–Deficient Mice
Authors: J örg Koglin, Troels Glysing-Jensen, John S. Mudgett, Mary E. Russell
Journal: Circulation (1998)

Background —Inducible NO synthase (NOS2, or iNOS) is upregulated in grafts with transplant arteriosclerosis. However, the functional role of NOS2 in the pathogenesis of transplant arteriosclerosis remains unclear. NOS2 may regulate lesion development by modulating the early alloimmune response and/or late myointimal thickening. Methods and Results —To determine whether NOS2-mediated pathways protect against or promote transplant arteriosclerosis, we used NOS2-deficient mice as recipients in our vascularized chronic cardiac rejection model. The severity of vascular thickening in 55-day grafts placed into NOS2 −/− recipients (n=13) was compared with that in wild-type recipients (n=15). Computer-assisted analysis of all elastin-stained vessels (n=283) showed significantly increased luminal occlusion (77.1±9.4% versus 40.8±13.6%, P &lt;.0001) and intima/media ratios in allografts from NOS2 −/− recipients (1.9±1.3 versus 0.4±0.3, P =.0002). To elucidate potential mechanisms, we studied NOS2 effects on T-cell differentiation (Th 1 /Th 2 ) and neointimal smooth muscle cell accumulation. Normalized mRNA levels for Th 1 - (signal transducer and activator of transcription [STAT] 4, interleukin [IL]-2, interferon-γ) and Th 2 - (STAT 6, IL-4, and IL-5) associated factors were comparable in both groups. In contrast, quantitative analysis of the α-actin–positive area showed a significant increase in the contribution of smooth muscle cells within the neointima in allografts from NOS2 −/− recipients (28.2±2.0%) compared with wild-type controls (13.2±2.3%; P &lt;.0001). Conclusions —NOS2 plays a protective role in the development of transplant arteriosclerosis, suppressing neointimal smooth muscle cell accumulation.
Initial and six-month results of gradual and prolonged balloon angioplasty in small coronary arteries: a randomized comparison with cutting balloon angioplasty and conventional balloon angioplasty
Authors: Hisashi Umeda, Ken Sawada, Masaki Yamauchi, Hirokazu Iwata, Toru Tajika, Yosuke Murase, Akihiro Hirashiki, Toshikazu Tanaka, Hirohumi Kanda, Masaki Yamauchi, Hirokazu Iwata, Hitoshi Ishihara, Mitsuhiro Yokota, Mitsunori Iwase
Journal: Journal of the American College of Cardiology (2002)
The value of in-patient dermatology: a survey of in-patients in Scotland and northern England
Authors: None MUNRO, None LOWE, None MCLOONE, None WHITE, None HUNTER
Journal: British Journal of Dermatology (1999)

Dermatology in-patient units are frequently threatened with reduction or closure, yet there are few objective data regarding the nature and use of in-patient management with which to assess their value. We have surveyed 300 patients admitted during March 1997 to dermatology units throughout Scotland and Northern England, to establish their clinical and social profile, and the outcome of admission. All departments provided phototherapy and out-patient treatment services, and 84% of those admitted lived within an hour's travel of one of these. Three diagnostic groups (psoriasis, eczema and leg ulcers) accounted for 83% of in-patient days. Patients were admitted principally because of disease severity but many, including half of those with psoriasis, had concurrent medical problems such as alcohol abuse, psychiatric disorder or arthropathy. Many patients with psoriasis and leg ulcers were from socially deprived areas, as defined by low Carstairs index scores, and a similar proportion received income support. Eighteen per cent of patients, mainly those with acute disorders, would have needed admission irrespective of dermatology bed availability. Out-patient management was considered the next best alternative for only 28% of patients, and many patients would have been expected to treat themselves. By contrast, 84% of patients admitted were cleared or substantially improved, or had procedures completed as planned, and another 12% were partially improved. Outcomes were particularly good in psoriasis, eczema and infection groups. We have demonstrated that in-patient management is highly effective in providing remission in chronic skin disease, and our survey also suggests that concomitant disability or social factors mean that for many such patients ambulatory care cannot replace this service.
Racial/Ethnic Differences in Dyslipidemia Patterns
Authors: Ariel T.H. Frank, Beinan Zhao, Powell O. Jose, Kristen M.J. Azar, Stephen P. Fortmann, Latha P. Palaniappan
Journal: Circulation (2013)

Background— No studies have comprehensively examined the prevalence of dyslipidemia, a major risk factor for cardiovascular disease, among diverse racial/ethnic minority groups. The primary aim of this study was to identify racial/ethnic differences in dyslipidemia among minorities including Asian Americans (Asian Indian, Chinese, Filipino, Japanese, Korean, or Vietnamese), Mexican Americans, and blacks compared with non-Hispanic whites. Methods and Results— Using a 3-year cross section (2008–2011), we identified 169 430 active primary care patients (35 years or older) from an outpatient healthcare organization in northern California. Age-standardized prevalence rates were calculated for 3 dyslipidemia subtypes: high triglycerides (fasting laboratory value ≥150 mg/dL), low levels of high-density lipoprotein cholesterol (fasting laboratory value &lt;40 mg/dL [men] and &lt;50 mg/dL [women]), and high levels of low-density lipoprotein cholesterol (fasting laboratory value ≥130 mg/dL or taking low-density lipoprotein–lowering agents). Odds ratios were calculated by multivariable logistic regression, with adjustment for patient characteristics (age, measured body mass index, smoking). Compared with non-Hispanic whites, every minority subgroup had an increased prevalence of high triglycerides except blacks. Most minority groups had an increased prevalence of low high-density lipoprotein cholesterol, except for Japanese and blacks. The prevalence of high low-density lipoprotein cholesterol was increased among Asian Indians, Filipinos, Japanese, and Vietnamese compared with non-Hispanic whites. Conclusions— Minority groups, except for blacks, were more likely to have high triglyceride/low high-density lipoprotein cholesterol dyslipidemia. Further research is needed to determine how racial/ethnic differences in dyslipidemia affect racial/ethnic differences in cardiovascular disease rates.