tbuckley/cabot-search huggingface dataset:
Self-reported skin morbidity and mental health. A population survey among adults in a Norwegian city
Authors: F. Dalgard, A. Svensson, J. Sundby, O.S. Dalgard
Journal: British Journal of Dermatology (2005)

Background Several studies among dermatological patients have shown a link between various chronic dermatological diseases and mental morbidity. Objectives To explore the association between self‐reported skin morbidity and psychosocial factors in the general population. Methods This population‐based cross‐sectional study is part of the Oslo Health Study conducted during 2000–2001. All individuals in Oslo County, Norway, born in 1924/25, 1940/41, 1955, 1960 and 1970 received a postal questionnaire, which 18 770 men and women answered. The questionnaire provided information on sociodemographic factors and self‐reported health and psychosocial factors. Dichotomous variables for 10 self‐reported skin complaints were used. These were previously validated and refer to the most common chronic skin diseases. Mental distress was measured with a validated 10‐item instrument, the Hopkins Symptom Check List‐10; social support with the number of confidants; and negative life events with a 12‐item validated instrument. Results The odds ratio (OR) for mental distress was 1·70 [95% confidence interval (CI) 1·21–2·38] for having itch, 1·64 (95% CI 1·15–2·34) for pimples and 1·72 (95% CI 1·06–2·80) for face rash in an adjusted model. In an adjusted model the OR for skin disease was 1·60 (95% CI 1·39–1·84) when the individual had experienced more than two negative life events; and 2·52 (95% CI 2·12–3·00) for mental distress. Skin morbidity increased for both genders, with poor social support network. There was a significant interaction between social support network and negative life events in the logistic regression model for skin disease when adjusted for sociodemographic factors. Conclusions The study quantifies the association between dermatological problems and psychosocial factors at a population level. It underlines the need to focus on these issues in research and needs assessment in dermatology.
Drug survival of fumaric acid esters for psoriasis: a retrospective study
Authors: N. Ismail, P. Collins, S. Rogers, B. Kirby, A. Lally
Journal: British Journal of Dermatology (2014)

Fumaric acid esters (FAEs) have been used for over 30 years in the management of psoriasis.To determine drug survival of FAEs in patients with psoriasis, treatment-limiting adverse drug events and the range of effective drug doses.A retrospective, single-centre study assessing all patients commenced on FAEs between October 2003 and July 2012. Demographic data, length of treatment, reasons for discontinuation of FAEs, side-effects and range of doses were recorded.Two hundred and forty-nine patients [160 (64%) male] were included. The mean age at which FAEs were commenced was 44·5 years (range 17-82 years). The mean length of treatment was 28 months (range 1 week to 106 months). In patients who were commenced on FAEs ≥ 4 years before inclusion in this study, the 4-year drug survival was 60% (64/107). FAEs were discontinued in 146/249 patients (59%); this was due to lack of efficacy in 59/146 (40%) and gastrointestinal upset in 39/146 (27%). A very low dose of FAEs (< 240 mg daily) was successful in maintaining control of psoriasis in 26 (10%) patients. The mean treatment duration of these patients was 64 months (range 32-106 months).Fumaric acid esters have a 4-year drug survival rate of 60%, which compares favourably with reported 4-year survival rates of 40% for etanercept and adalimumab and 70% for infliximab. Longer drug survival is more likely in the significant subgroup of patients in whom a very low dose of FAEs is sufficient to control disease. The reasons for this are unclear.
Angiotensin II Activates pp60 <sup>c-</sup> <sup>src</sup> in Vascular Smooth Muscle Cells
Authors: Mari Ishida, Mario B. Marrero, Bernhard Schieffer, Takafumi Ishida, Kenneth E. Bernstein, Bradford C. Berk
Journal: Circulation Research (1995)

Abstract The angiotensin II type-1 (AT 1 ) receptor, a G protein–coupled receptor, lacks intrinsic kinase activity. However, recent data show that angiotensin II (Ang II) stimulates tyrosine phosphorylation of phospholipase C-γ1 (PLC-γ1), Stat91 (one of the signal transducers and activators of transcription), and paxillin in vascular smooth muscle cells. The tyrosine kinases responsible for these phosphorylation events are unknown. Src family kinases have been shown to phosphorylate PLC-γ1 and to be activated by G protein–coupled receptors. We hypothesized that pp60 c- src associates with the AT 1 receptor and is activated after Ang II stimulation of smooth muscle cells. We immunoprecipitated pp60 c- src from Ang II–stimulated vascular smooth muscle cells and measured pp60 c- src activity by autophosphorylation and by phosphorylation of enolase. Both assays demonstrated an approximately threefold increase in pp60 c- src activity within 1 minute. A similar increase in Ang II–stimulated pp60 c- src activity was observed in Chinese hamster ovary cells transfected with the AT 1 receptor but not in untransfected cells. These data are the first to show that pp60 c- src is activated by Ang II. To determine if pp60 c- src associated with the AT 1 receptor, the AT 1 receptor was immunoprecipitated (with two different antibodies), and Western blots were performed with two different anti-pp60 c- src antibodies. No pp60 c- src was detected. In addition, direct interaction between the AT 1 receptor and pp60 c- src could not be demonstrated by using a glutathione S-transferase (GST)-AT 1 fusion protein to bind proteins from cell lysates stimulated by Ang II. In combination with recent findings that anti-pp60 c- src antibodies inhibit Ang II–mediated PLC-γ1 phosphorylation, our data suggest an important role for pp60 c- src in Ang II signal transduction.
Relationship of cardiac oxygen usage, adenosine content, and coronary resistance in dogs.
Authors: D Saito, D G Nixon, R B Vomacka, R A Olsson
Journal: Circulation Research (1980)

Analysis of the relationships between cardiac oxygen usage (MVO2), cardiac muscle adenosine levels([Ado]), and coronary vascular resistance (R) in open-chest, anesthetized dogs tested the hypothesis that adenosine is a physiological regulator of coronary flow. Experiments using each dog as its own control showed that [Ado] varied directly with MVO2 as the latter changed spontaneously or in response to atrial pacing, paired pacing, aortic constriction, of beta-adrenergic blockade. In turn, R varied inversely with changes in [Ado]. Stimulating MVO2 with isoproterenol significantly increased the slope of the regression of [Ado] on MVO2 as well as of R-1 on [Ado]. The effect of beta-adrenergic stimulation on [Ado] is unexplained, but its effect on R-1 seems to reflect the combined effects of adenosine and direct beta-adrenergic coronary relaxation. These results support the hypothesis that adenosine mediates the coronary flow responses to changes in MVO2.
hPuf-A/KIAA0020 Modulates PARP-1 Cleavage upon Genotoxic Stress
Authors: Hao-Yen Chang, Chi-Chen Fan, Po-Chen Chu, Bo-En Hong, Hyeon Jeong Lee, Mau-Sun Chang
Journal: Cancer Research (2011)

Human hPuf-A/KIAA0020 was first identified as a new minor histocompatibility antigen in 2001. Its zebrafish orthologue contains six Pumilio-homology RNA-binding domains and has been shown to participate in the development of eyes and primordial germ cells, but the cellular function of hPuf-A remains unclear. In this report, we showed that hPuf-A predominantly localized in the nucleoli with minor punctate signals in the nucleoplasm. The nucleolar localization of hPuf-A would redistribute to the nucleoplasm after the treatment of RNA polymerase inhibitors (actinomycin D and 5,6-dichlorobenzimidazole riboside) and topoisomerase inhibitors [camptothecin (CPT) and etoposide]. Interestingly, knockdown of hPuf-A sensitized cells to CPT and UV treatment and cells constitutively overexpressing hPuf-A became more resistant to genotoxic exposure. Affinity gel pull-down coupled with mass spectrometric analysis identified PARP-1 as one of the hPuf-A interacting proteins. hPuf-A specifically interacts with the catalytic domain of PARP-1 and inhibits poly(ADP-ribosyl)ation of PARP-1 in vitro. Depletion of hPuf-A increased the cleaved PARP-1 and overexpression of hPuf-A lessened PARP-1 cleavage when cells were exposed to CPT and UV light. Collectively, hPuf-A may regulate cellular response to genotoxic stress by inhibiting PARP-1 activity and thus preventing PARP-1 degradation by caspase-3.
Fertility Following Oral Contraception
Authors: William Winner
Journal: JAMA (1965)

To the Editor:—  It has been widely suggested that following termination of a course of oral contraception, a woman's fertility potential (ie, her ability to conceive) can be expected to increase. Indeed, these drugs have been used by many physicians as part of the treatment of infertility.  Reevaluation of the available information yields the following data pertinent and basic to these concepts:  The evidence that oral contraception may produce an improvement in a woman's fertility potential has received statistical support. To test the relationship to subsequent fertility, each of these several surveys used as the study group patients who discontinued oral contraception in order to attempt conception. Each survey, however, used the same reference group—a group of women who had used a variety of mechanical or chemical methods of contraception prior to a planned pregnancy.5The pertinent data available are summarized in Table I.  As observed by Goldzieher,4
Intratumoral injection of <i>Clostridium novyi</i> -NT spores induces antitumor responses
Authors: Nicholas J. Roberts, Linping Zhang, Filip Janku, Amanda Collins, Ren-Yuan Bai, Verena Staedtke, Anthony W. Rusk, David Tung, Maria Miller, Jeffrey Roix, Kristen V. Khanna, Ravi Murthy, Robert S. Benjamin, Thorunn Helgason, Ariel D. Szvalb, Justin E. Bird, Sinchita Roy-Chowdhuri, Halle H. Zhang, Yuan Qiao, Baktiar Karim, Jennifer McDaniel, Amanda Elpiner, Alexandra Sahora, Joshua Lachowicz, Brenda Phillips, Avenelle Turner, Mary K. Klein, Gerald Post, Luis A. Diaz, Gregory J. Riggins, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Chetan Bettegowda, David L. Huso, Mary Varterasian, Saurabh Saha, Shibin Zhou
Journal: Science Translational Medicine (2014)

Clostridium novyi -NT targets aberrant tumor physiology and can produce a precise, robust, and reproducible antitumor response.
Glutamate Levels in the Associative Striatum Before and After 4 Weeks of Antipsychotic Treatment in First-Episode Psychosis
Authors: Camilo de la Fuente-Sandoval, Pablo León-Ortiz, Mariana Azcárraga, Sylvana Stephano, Rafael Favila, Leonardo Díaz-Galvis, Patricia Alvarado-Alanis, Jesús Ramírez-Bermúdez, Ariel Graff-Guerrero
Journal: JAMA Psychiatry (2013)

Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown.To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects.Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking.Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment.Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel.Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks.Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment. These results provide support for the hypothesis that improvement in clinical symptoms might be related to a decrease in glutamate levels.
Activation of human B lymphocytes. I. Direct plaque-forming cell assay for the measurement of polyclonal activation and antigenic stimulation of human B lymphocytes.
Authors: A S Fauci, K R Pratt
Journal: The Journal of Experimental Medicine (1976)

A model for the detection of single cell antibody production by human tonsillar lymphocytes after stimulation with either sheep red blood cells (SRBC) or polyclonal B-cell activators has been described. The culture system is a modified Mishell-Dutton technique with certain critical factors identified. The assay is a sensitive and resproducible hemolysis-in-gel system employing an ultra-thin layer gel technique measuring plaque-forming cells (PFC) against SRBC targets. Several factors essential for optimal responses are described, but the critical feature of the culture system is the use of selected lots of human AB serum supplements which are extensively absorbed with SRBC. This removes a blocking factor present in most human serum which suppresses the B-cell response to SRBC targets after stimulation with either SRBC or several polyclonal B-cell activators. In addition, absorption of serum with SRBC eliminates the presence of artifactual plaques. Background PFC are extremely low and stimulated cultures show significant and reproducible responses. These studies provide a simple, sensitive, and reproducible model for probing the complex events associated with activation of human B lymphocytes.
Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine.
Authors: A M de Silva, S R Telford, L R Brunet, S W Barthold, E Fikrig
Journal: The Journal of Experimental Medicine (1996)

Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. A vaccine based on B. burgdorferi outer surface protein (Osp) A protects mice from spirochete infection. Here we report on the expression of OspA on spirochetes inside engorging ticks and relate OspA expression to antispirochetal immunity. Spirochetes in the gut of unfed nymphal ticks were stained by an OspA antibody, whereas in feeding ticks, the majority of spirochetes in the gut and salivary glands did not stain with the antibody. Thus, OspA was not expressed on most spirochetes during transmission from the vector to the vertebrate host. To examine the mechanism of protection afforded by OspA antibody, mice were passively immunized with OspA antibody at different times relative to tick attachment. When OspA antibody was administered to mice before or at the time of tick attachment, spirochetal development events in the vector, such as growth and salivary gland invasion, were blocked and the mice were protected from B. burgdorferi infection. When OspA antibody was administered to mice 48 h after tick attachment, spirochetes persisted in the nymphs and the mice were not protected despite the presence of circulating antibodies in the host as well as in the tick blood meal. Thus, OspA immunity appears to be effective only during a narrow window time at the beginning of the blood meal when antibodies bind to OspA-expressing spirochetes in the tick gut and block transmission from the vector to the host.
Termination of Ventricular Tachycardia in the Human Heart
Authors: Steven M. Pogwizd, Mina K. Chung, Michael E. Cain
Journal: Circulation (1997)

Background To define the electrophysiological basis for the termination of ventricular tachycardia (VT), three-dimensional cardiac mapping and analysis of the terminal beats of nonsustained VT and beats of sustained VT were performed in six patients with healed myocardial infarcts. Methods and Results Termination of VT was due to activation from multiple initiation sites that were discordant from those responsible for the maintenance of sustained VT in 45% of cases, to repetitive activation from single sites that were discordant from those responsible for the maintenance of sustained VT in 24% of cases, or to activation from sites concordant with the sites of repetitive activation during sustained VT in 31% of cases. Sustained VT was characterized by occasional shifting of initiation sites, even after the tachycardia entered the stable monomorphic phase. Mapping was of sufficient density to define the mechanisms for 21 terminating beats of VT. In 5 cases, termination was due to intramural reentry, which initiated with the total activation time of the preceding beat of 204±11 milliseconds (ms) but terminated primarily because of a decrease in total activation time (144±23 ms, P =.03) that was associated with the development of intramural conduction block or with significant changes in the activation sequence along the reentrant circuit. In 16 cases, terminal beats were initiated by a focal mechanism on the basis of the absence of intervening electrical activity from the termination of the preceding beat to the initiation of the terminating beat (172±9 ms). Focal activation was associated with less conduction delay of the preceding beat (115±6 ms) than terminating reentrant beats ( P &lt;.001) and usually terminated suddenly without oscillations in cycle length or total activation time. Conclusions Termination of VT is associated with alterations in initiation sites that are most often discordant from those maintaining sustained VT and is due to either reentrant or focal mechanisms.
Skeletal Muscle Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase Gene Expression in Congestive Heart Failure
Authors: David G. Peters, Heather L. Mitchell, Sylvia A. McCune, Sonhee Park, Jay H. Williams, Susan C. Kandarian
Journal: Circulation Research (1997)

Abstract Congestive heart failure leads to skeletal muscle abnormalities, one of which is a prolongation of sarcoplasmic reticulum Ca 2+ flux. The purpose of this study was to determine whether skeletal muscle of spontaneous hypertensive and heart failure rats have alterations in the expression of the sarcoplasmic (or endoplasmic) reticulum Ca 2+ -ATPase (SERCA) gene. Northern analysis revealed that SERCA1, the predominant skeletal muscle isoform, was decreased by 45%, 43%, and 58% in the tibialis anterior, plantaris, and diaphragm muscles, respectively. Ribonuclease protection assay showed that the decrease was due to the adult isoform, SERCA1a, with minor changes in the alternatively spliced neonatal isoform, SERCA1b. There was no change in SERCA1 mRNA levels in gastrocnemius muscles. No change was found in SERCA2a (cardiac/slow skeletal isoform) mRNA or protein levels or in SERCA2b (smooth muscle isoform), dihydropyridine receptor, or α-actin mRNA levels in diaphragm muscle. Northern blot and ribonuclease protection assays showed that SERCA2a decreased 61% in the heart while the alternatively spliced isoform, SERCA2b, decreased 27%. Western analysis of the tibialis anterior, diaphragm, and gastrocnemius muscles showed a decrease in SERCA1 protein levels by 46%, 64%, and 42%, respectively, whereas sarcoplasmic reticulum Ca 2+ -ATPase activity, a functional correlate of SERCA expression, was decreased by 38%, 38%, and 40% in the same muscles. SERCA2 protein expression decreased by 36% in the failing heart. Decreases in both mRNA and protein suggest pretranslational control of SERCA1 expression, whereas the lack of decreased SERCA1 mRNA in gastrocnemius muscle suggests translational regulation. The decreased SERCA1 protein expression in all muscles studied probably contributes to contractile abnormalities related to excitation-contraction coupling function in heart failure.
Chronic and slowly progressive weakness of the legs and hands
Authors: H. Nightingale, G. Pfeffer, R. Horvath
Journal: BMJ (2014)

A 59 year old man was referred for a definitive diagnosis of chronic and progressive bilateral weakness of his feet and legs, which began aged 11 years. This was associated with gradual clawing of his feet, bilateral hand weakness, bilateral mild numbness of his hands and feet, and foot pain. No bladder or bowel disturbance was reported.

His sister, father, and paternal grandmother also had onset of similar symptoms in childhood.

On examination we found no cranial nerve abnormality. Tone was normal throughout. He had a postural upper limb tremor and Medical Research Council (MRC) grade 4/5 weakness and wasting of the intrinsic muscles of the hand. He also had bilateral pes cavus, wasting of the calf muscles (figure⇓), and MRC grade 4/5 weakness of hip and knee flexion and extension and 3/5 weakness in the feet. Achilles tendon reflexes were absent but remaining deep tendon reflexes were normal with downgoing plantar responses. Mild sensory loss to pinprick was present below the elbows and knees. Vibration sensation was reduced below the ankles, proprioception was normal throughout, and the Romberg test was negative. No cerebellar dysfunction was detected. He had a high stepping gait.



Pes cavus and wasting of the calf muscles in this patient



Nerve conduction studies showed reduced compound muscle and sensory nerve action potential amplitudes with well preserved velocities.



### 1 What do the clinical examination and nerve conduction studies indicate?

#### Short answer

An axonal sensorimotor neuropathy.

#### Long answer

Axonal damage results in reduced amplitude of the compound muscle and sensory nerve action potentials, which are generated by muscle fibre activation from the stimulated nerve.1 By contrast, demyelination slows …
Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat.
Authors: V J Quagliarello, A Ma, H Stukenbrok, G E Palade
Journal: The Journal of Experimental Medicine (1991)

Injury to the blood brain barrier (BBB) is a fundamental sequela of bacterial meningitis, yet the precise mechanism facilitating exudation of albumin across the endothelium of the cerebral microvasculature remains conjectural. After intracisternal inoculation of Escherichia coli (0111:B4) lipopolysaccharide in rats to elicit a reversible meningitis and BBB injury, we utilized in situ tracer perfusion and immunolabeling procedures to identify by transmission electron microscopy the precise topography and microvascular exit pathway(s) of bovine serum albumin (BSA). Results revealed that during meningitis there was: (a) an inducible increase in immunodetectable monomeric BSA binding to the luminal membrane of all microvascular segments in the pia-arachnoid and superficial brain cortex; (b) similar uptake of both colloidal Au-BSA (as well as monomeric BSA) by plasmalemmal vesicles but no detectable transcytosis to the abluminal side; and (c) predominant exit of both perfused Au-BSA and immunodetectable monomeric BSA through open intercellular junctions of venules in the pia-arachnoid. This was corroborated in separate experiments documenting focal pial venular leaks of in situ perfused 0.01% colloidal carbon black during experimental meningitis. These results provide precise localization of BBB injury in meningitis to meningeal venules, confirm a paracellular exit pathway of albumin via open intercellular junctions, and suggest an injury mechanism amenable to specific therapeutic intervention.