tbuckley/cabot-search huggingface dataset:
Cellular cytotoxicity against autologous hepatocytes in acute and chronic non-A, non-B hepatitis.
Authors: T Poralla, T H Hutteroth, K H Meyer zum Buschenfelde
Journal: Gut (1984)

In a microcytotoxicity assay we tested lymphocyte cytotoxicity against autologous hepatocytes. The following cytotoxicity values were found (given mean +/- SEM): acute non-A, non-B (NANB) hepatitis 45.7 +/- 4.3% (n = 7), chronic NANB hepatitis 32.8 +/- 5.1% (n = 11), chronic active hepatitis B (CAH-B) 27.7 +/- 6.7% (n = 10), toxic lesions 18.1 +/- 4.2% (n = 18), controls with normal liver histology or minimal changes 4.9 +/- 2.5% (n = 8). Thus our study shows enhanced cellular cytotoxicity in acute and chronic NANB hepatitis and indicates that T cells as well as non-T cells have cytotoxic effector functions. These findings are similar to those obtained in CAH-B and suggest that cellular immune reactions play an important role in the course of NANB hepatitis. For comparison we tested cytotoxic reactions in toxic lesions. They were only moderate and well distinguishable from those observed in NANB hepatitis and CAH-B; they even may be unspecific. No correlation was seen between cytotoxicity and aminotransferase concentrations.
Combined Pharmacotherapy and Psychotherapy as Maintenance Treatment for Late-Life Depression: Effects on Social Adjustment
Authors: Eric J. Lenze, Mary Amanda Dew, Sati Mazumdar, Amy E. Begley, Cleon Cornes, Mark D. Miller, Stanley D. Imber, Ellen Frank, David J. Kupfer, Charles F. Reynolds
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study examined the effects of maintenance treatment for late-life depression on social adjustment. The authors hypothesized that elderly patients recovering from depression would have better social adjustment with medication and interpersonal psychotherapy than with medication or psychotherapy alone. METHOD: Patients aged 60 and older recovering from recurrent major depression were randomly assigned to one of four treatments: nortriptyline and interpersonal psychotherapy, nortriptyline and clinic visits, placebo and psychotherapy, or placebo and clinic visits. The Social Adjustment Scale was administered every 3 months until illness recurrence. Combined treatment was compared to monotherapy on scores over 1 year among patients who remained in recovery (N=49). RESULTS: Patients receiving nortriptyline and interpersonal psychotherapy maintained social adjustment, which declined in those receiving monotherapy. CONCLUSIONS: Treatment of late-life depression with nortriptyline and psychotherapy is more likely to maintain social adjustment than treatment with either alone. Combination therapy improves not only duration but quality of wellness.
Phosphorylated and Nonphosphorylated Serine and Threonine Residues Evolve at Different Rates in Mammals
Authors: S. C.-C. Chen, F.-C. Chen, W.-H. Li
Journal: Molecular Biology and Evolution (2010)

Protein phosphorylation plays an important role in the regulation of protein function. Phosphorylated residues are generally assumed to be subject to functional constraint, but it has recently been suggested from a comparison of distantly related vertebrate species that most phosphorylated residues evolve at the rates consistent with the surrounding regions. To resolve the controversy, we infer the ancestral phosphoproteome of human and mouse to compare the evolutionary rates of phosphorylated and nonphosphorylated serine (S), threonine (T), and tyrosine (Y) residues. This approach enables accurate estimation of evolutionary rates as it does not assume deep conservation of phosphorylated residues. We show that phosphorylated S/T residues tend to evolve more slowly than nonphosphorylated S/T residues not only in disordered but also in ordered protein regions, indicating evolutionary conservation of phosphorylated S/T residues in mammals. Thus, phosphorylated S/T residues tend to be subject to stronger functional constraint than nonphosphorylated residues regardless of the protein regions in which they reside. In contrast, phosphorylated Y residues evolve at similar rates as nonphosphorylated ones. We also find that the human lineage has gained more phosphorylated T residues and lost fewer phosphorylated Y residues than the mouse lineage. The cause of the gain/loss imbalance remains a mystery but should be worth exploring.
PLASMA HEME OXYGENASE-1 LEVEL IS ASSOCIATED WITH THE PRESENCE OF CORONARY ARTERY DISEASE AND UNSTABLE CLINICAL PRESENTATION
Authors: William Chan, Swati Mukherjee, Bronwyn A. Kingwell, Anthony J. White, James A. Shaw, Alaina Natoli, Beth Johnson, Anthony S. Walton, Anthony M. Dart, Stephen J. Duffy
Journal: Journal of the American College of Cardiology (2010)
African cycling: dormant to dominant?
Authors: Jarrad Van Zuydam, Jonathan Patricios
Journal: British Journal of Sports Medicine (2015)

That is the current world marathon record for men.Since 1960 the record has fallen regularly and the 2 hour mark is now talked about as a target rather than a barrier.African distance runners have repeatedly lowered this record, especially in the past decade.Among the 100 fastest marathon times ever, 99 are by African-born athletes.
Bivalirudin for Patients with Acute Coronary Syndromes
Authors: Gregg W. Stone, Brent T. McLaurin, David A. Cox, Michel E. Bertrand, A. Michael Lincoff, Jeffrey W. Moses, Harvey D. White, Stuart J. Pocock, James H. Ware, Frederick Feit, Antonio Colombo, Philip E. Aylward, Angel R. Cequier, Harald Darius, Walter Desmet, Ramin Ebrahimi, Martial Hamon, Lars H. Rasmussen, Hans-Jürgen Rupprecht, James Hoekstra, Roxana Mehran, E. Magnus Ohman
Journal: New England Journal of Medicine (2006)

Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients.We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding.Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P=0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P=0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97).In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158 [ClinicalTrials.gov].).
On the Real Value of Blood-Letting in Acute Diseases
Authors: A. W. Barclay
Journal: BMJ (1859)

proximity to the part operated upon; and that that reflexion is not, as the anterior reflexion on to the abdominal parietes is, moveable with the distension of the walls of the bladder.So that there is no more (or, at any rate, not much more) room when the bladder is full than when it is empty.Perhaps, however, the danger from that source has been exaggerated, since the puncture is always made through a part of the rectum where the bulging fluctuating tumour formed by the enlarged bladder is felt; and this point cannot, of course, be behind the peritoneum.In the present case, the operation seems to have been quite successful in attaining the object proposed, which was merely to spare the patient pain during the few last days of his life, as he was evidently dying on his admission. III. DISLOCATION OF THE HIP AT A VERY EARLY AGE.Under the care of E. Cumxn, Esq.Jane B., a little girl, 4 years of age last November, was ad.mitted under the care of Mr. Cutler on January 31st, on ac- count of an accident in which she had been knocked down by a carriage, which was supposed to have passed over her, though this latter fact seemed doubtful.On admission, all the symp.toms of dislocation of the right hip on to the dorsum ilii were apparent.The extremity was shortened to the 'extent of nearly two inches; the pelvis was in its natural position; the foot pointing across that of the opposite side.There was no orepitus on making pressure on the femur, and the head of the bone could be indistinetly felt under the gluteal muscles.The child was put under the influence of chloroform, and then re- uction was very easily effected by extension with the hand.The hone slipped into its place with the peculiar sensation which attends the reduction of a dislocation, and the length of the limb was permanently restored.The child's legs were bandaged together, and she was kept in bed for a fortnight.Slhe was discharged on February 23rd, walking quite well, though with a little stiffness.EsiAaKs.The present is the earliest case of dislocation of the hip which we remember to have read of, and is therefore put on record as a fact which deserves mention.Mr. Erichsen -says that Travers met with a dislocation of the hip in a child five years of age.If this means, as it probably does, between five and six., the patient would bave been about a year older than the little girl who was the subject of the present accident.
Highly PEGylated DNA Nanoparticles Provide Uniform and Widespread Gene Transfer in the Brain
Authors: Panagiotis Mastorakos, Clark Zhang, Sneha Berry, Yumin Oh, Seulki Lee, Charles G. Eberhart, Graeme F. Woodworth, Jung Soo Suk, Justin Hanes
Journal: Advanced Healthcare Materials (2015)

Gene delivery to the central nervous system (CNS) has potential as a means for treating numerous debilitating neurological diseases. Nonviral gene vector platforms are tailorable and can overcome key limitations intrinsic to virus‐mediated delivery; however, lack of clinical efficacy with nonviral systems to date may be attributed to limited gene vector dispersion and transfection in vivo. It is shown that the brain extracellular matrix (ECM) strongly limits penetration of polymer‐based gene vector nanoparticles (NP) through the brain parenchyma, even when they are very small (&lt;60 nm) and coated with a polyethylene glycol (PEG) corona of typical density. Following convection enhanced delivery (CED), conventional gene vectors are confined to the injection site, presumably by adhesive interactions with the brain ECM and do not provide gene expression beyond the point of administration. In contrast, it is found that incorporating highly PEGylated polymers allows the production of compacted (≈43 nm) and colloidally stable DNA NP that avoid adhesive trapping within the brain parenchyma. When administered by CED into the rat striatum, highly PEGylated DNA NP distribute throughout and provide broad transgene expression without vector‐induced toxicity. The use of these brain‐penetrating gene vectors, in conjunction with CED, offers an avenue to improve gene therapy for CNS diseases.
Cyclo-oxygenase-2 inhibitors and COPD: a bright spot?
Authors: R M Effros
Journal: Thorax (2005)

<h3></h3> Transition from paediatric to adult services is a challenging process and developing rare, life-threatening, lifelong illness around this time adds significant complexity. Sheffield has a seamless adolescent rheumatology service spanning both paediatric and adult hospitals, aiming to provide developmentally appropriate healthcare (DAH). To exemplify the benefits of this approach, we present two adolescents with the rare combination of large vessel vasculitis and inflammatory bowel disease. Case A was diagnosed in the Children’s hospital and B in adult services, within 1 month of each other. Within the seamless service we were able to coordinate a patient-centred approach both for complex medicines management and ongoing clinical care. <i>A:</i> 17 year-old male with complex inflammatory bowel disease since age 2. Treated with oral steroids with poor response to multiple DMARDs, biologics and elemental nutrition. Health professionals doubted good adherence and he needed extensive input. Vedolizumab was started in 2019 with improvement of gut symptoms but subsequent investigation of neck pain revealed stenotic large vessel vasculitis (LVV) and a diagnosis of Takayasu arteritis was made. <i>B:</i> 17 year-old male with ulcerative colitis, diagnosed aged 14. Treated with infliximab and azathioprine when transferred to adult gastroenterology services. Atypical symptoms developed in 2019 and chest CT/PET-CT confirmed LVV (Takayasu arteritis). LVV is a rare, life-threatening condition. Well-established team working enabled sharing of paediatric and adult rheumatology and gastroenterology experience. This enabled rational, tailored treatment plans to be devised through shared professional expertise – A has stopped vedolizumab and started tocilizumab, B has started adalimumab and both started methotrexate. LVV needs lifetime monitoring. Planning for that monitoring (imaging, serology, biopsychosocial care) in adult services is therefore an important part of initial management. A and B are at different developmental stages. Our service enables DAH with A remaining in paediatrics, but with care planned to facilitate transition and ongoing management in adult services, B continues in adult services with the benefit of paediatric experience in managing Takayasu arteritis. ‘Adolescent responsive services’ are key in developmentally appropriate healthcarecare. The Sheffield Seamless Adolescent Rheumatology service is an example of this in practice.
Acknowledgment and Apology: Text Copied from <i>Biochemical Journal</i>
Authors: Kamel Izeradjene, Leslie Douglas, Addison Delaney, Janet A. Houghton
Journal: Clinical Cancer Research (2005)

To the Editor: 

This letter serves as an acknowledgment that in the Introduction section of our article on the influence of casein kinase II on human rhabdomyosarcoma cells published in Clinical Cancer Research ([1][1]), the text of paragraph 2, lines 7 through 42 on page 6651 was directly copied
Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage
Authors: James A.P. Tomlinson, Ben Caplin, Olga Boruc, Claire Bruce-Cobbold, Pedro Cutillas, Dirk Dormann, Peter Faull, Rebecca C. Grossman, Sanjay Khadayate, Valeria R. Mas, Dorothea D. Nitsch, Zhen Wang, Jill T. Norman, Christopher S. Wilcox, David C. Wheeler, James Leiper
Journal: Journal of the American Society of Nephrology (2015)

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function.
The comparative effectiveness of anti-TNF therapy and methotrexate in patients with psoriatic arthritis: 6 month results from a longitudinal, observational, multicentre study
Authors: M S Heiberg, C Kaufmann, E Rodevand, K Mikkelsen, W Koldingsnes, P Mowinckel, T K Kvien
Journal: Annals of the Rheumatic Diseases (2007)

To compare the response to treatment with tumour necrosis factor (TNF) inhibitors and methotrexate (MTX) monotherapy in patients with psoriatic arthritis (PsA) within a real-life clinical setting.We analysed data from an ongoing longitudinal, observational multicentre study in Norway. Our data comprised 526 cases of patients with PsA who received either anti-TNF treatment (n = 146) or MTX monotherapy (n = 380) and were followed for at least 6 months with measures of disease activity, health status and utility scores. A propensity score was computed to adjust for channelling bias. The changes in measures of disease activity and health-related quality of life from baseline to 3- and 6-month follow-up were compared between the groups with adjustments for the baseline value of the dependent variable and the propensity score (analyses of covariance (ANCOVA)).The groups were significantly different at baseline with respect to demographic and disease activity measures. The variables included in the propensity score were age, sex, number of previous disease modifying anti-rheumatic drugs (DMARDs), presence of erosive disease, treatment centre and investigator's global assessment. The adjusted changes at 6 months were significantly larger in the anti-TNF group for ESR, DAS-28, M-HAQ, patient's assessments of pain, fatigue and global disease activity on a visual analogue scale (VAS) and 4 out of 8 SF-36 dimensions.Clinical improvement was superior with TNF inhibitors compared to MTX monotherapy in patients with PsA, when assessed in this setting of daily clinical practice.
Haemophilus influenzae lobar pneumonia in the father of a child with epiglottitis
Authors: H Manji, P Reeve
Journal: European Respiratory Journal (1990)

We present a case of Haemophilus influenzae lobar pneumonia in the father of a child admitted with acute epiglottitis caused by the same organism. The suggestion that adult, as well as child, contacts for Haemophilus influenzae epiglottitis should be prophylactically treated is discussed.
Chronic haemolysis after Lillehei-Kaster valve replacement. Comparison with the findings after Bjork-shiley and Starr-Edwards mitral valve replacement.
Authors: K M Rao, P A Learoyd, R S Rao, S M Rajah, D A Watson
Journal: Thorax (1980)

Nineteen female and sixteen male patients who have had their heart valves replaced with Lillehei-Kaster valves were investigated for haemolysis four to 18 months after operation. Investigation included serum lactic dehydrogenase, serum haptoglobins, and urine haemosiderin. Red cells survival, using autologous red cells labelled with 51Cr, was measured in 12 patients. No patient showed manifest anaemia. The serum lactic dehydrogenase levels were raised in 66% of the mitral valve patients, 81% of the aortic valve patients, and in all the double valve patients. The serum haptoglobins were decreased in 66% of mitral patients, 68% of aortic valve patients, and in 75% of the double valve patients. All the 12 patients studied had lower than normal red cell survivals. No correlation was found between the incidence of haemolysis and the size of the valve. In isolated mitral valve replacement 66% showed compensated haemolysis compared with 42% in Björk-Shiley valves (p less than 0.05), 85% in Starr-Edwards valves (composite seat) (p less than 0.01), and none in frame-mounted irradiated homografts (previous study) (p less than 0.001).
Diminished Suppression of the P50 Auditory Evoked Potential in Bipolar Disorder Subjects With a History of Psychosis
Authors: Ann Olincy, Laura Martin
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: People with schizophrenia, schizoaffective disorder, and bipolar illness share clinical symptoms, biological findings, and genetic susceptibility. Diminished suppression of the P50 auditory evoked potential is a phenotype used in studies of genetic susceptibility in schizophrenia. In patients with acute mania, this inhibitory deficit has been correlated with severity of clinical symptoms. This study addresses whether diminished P50 auditory evoked potential suppression represents a phenotype associated with psychosis in bipolar illness. METHOD: The P50 auditory evoked potential response to paired stimuli was measured in 64 subjects with bipolar illness. The Structured Clinical Interview for DSM-IV and a life chart determined diagnosis. The Beck Depression Inventory, Young Mania Rating Scale, and the Positive and Negative Syndrome Scale measured severity of current illness. Groups were compared with previously collected data from 36 schizophrenia patients and 42 healthy subjects. RESULTS: P50 suppression significantly differed between bipolar disorder patients with a lifetime history of psychosis and healthy subjects. P50 suppression in bipolar disorder patients without a history of psychosis did not differ from that of the healthy subjects. Severity of current symptoms did not correlate with P50 suppression. CONCLUSIONS: A longitudinal history of psychosis in subjects with bipolar illness was associated with diminished suppression of the P50 auditory evoked potential. This deficit may represent a common physiological mechanism associated with the vulnerability to psychosis in people with bipolar illness as well as in people with schizophrenia.
Dominant negative inhibitors of signalling through the phosphoinositol 3-kinase pathway for gene therapy of pancreatic cancer
Authors: V Stoll
Journal: Gut (2004)

Ras signalling is frequently aberrant in pancreatic cancer so that there is constitutive activation of the phosphatidylinositol 3-kinase (PI3K) and AKT/protein kinase B pathway, as well as the RAF/MEK/ERK pathway.In the present study we investigated the role of the PI3K/AKT pathway in malignant transformation of pancreatic cancer cells.A genetic approach was used to interfere with signal transduction in vitro and in vivo. RASN17, a dominant negative mutant of RAS, was applied to inhibit the PI3K/AKT pathway upstream of PI3K. The regulatory p85beta subunit of PI3K and the negative regulator PTEN were utilised to inhibit the pathway at the level of PI3K, and AAA-AKT, a dominant negative mutant of AKT was employed to interfere with PI3K/AKT signalling at the level of AKT.Antiproliferative, proapoptotic, and anticancer effects were documented, showing that inhibition of the PI3K pathway in these cell lines suppresses tumour cell growth in vitro and reduces growth in nude mice.The PI3K/AKT pathway represents a potential therapeutic target for pancreatic cancer, and gene therapy may be one approach to produce selective inhibition.