tbuckley/cabot-search huggingface dataset:
Fatal <i>Bacillus cereus</i> sepsis following resolving neutropenic enterocolitis during the treatment of acute leukemia
Authors: Amy S. Ginsburg, Lupe G. Salazar, Lawrence D. True, Mary L. Disis
Journal: American Journal of Hematology (2003)

Bacillus cereus is increasingly being acknowledged as a serious bacterial pathogen in immunosuppressed hosts. We report a case of fatal B. cereus sepsis in a patient with newly diagnosed acute leukemia following resolving neutropenic enterocolitis. Gastrointestinal complaints are common during induction chemotherapy, yet some antimicrobial coverage suitable for generalized neutropenia is not optimal for the eradication of B. cereus. This case demonstrates that, in the neutropenic patient with gastrointestinal complaints or in the setting of resolving neutropenic enterocolitis, it is important to anticipate possible B. cereus infection and sepsis.
Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure.
Authors: A B Haaber, I Eidemak, T Jensen, B Feldt-Rasmussen, S Strandgaard
Journal: Journal of the American Society of Nephrology (1995)

Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29 nondiabetic patients (GFR of 25 (11-44) mL/min x 1.73 m2 (median and range)) and 14 normal subjects. The proportion of smokers was similar between the groups. In the patients, the plasma concentration of von Willebrand factor was elevated by 61% (1.27 +/- 0.44 versus 0.79 +/- 0.28 U/mL; P < 0.01) (mean +/- SD) and that of fibrinogen was elevated by 72% (10.18 +/- 4.14 versus 5.92 +/- 2.01 mumol/L; P < 0.01). The plasma concentrations of lipoproteins showed an atherogenic pattern in the patients with increased levels of very low-density lipoprotein cholesterol (0.57 +/- 0.31 versus 0.33 +/- 0.13 mmol/L; P < 0.01) and triglycerides (1.26 +/- 0.25 versus 0.71 +/- 0.28 mmol/L; P < 0.01), but a decreased level of high-density lipoprotein cholesterol (1.23 +/- 0.33 versus 1.46 +/- 0.35 mmol/L; P < 0.05). Total cholesterol and low-density lipoprotein cholesterol were similar in the groups. The observed differences were further aggravated among smoking patients, particularly with respect to von Willebrand factor and triglycerides. The transcapillary escape rate of albumin was similar in the patients and the controls and was not correlated to the level of albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)
Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin
Authors: T. B. Huber
Journal: Journal of Clinical Investigation (2006)

Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular diagnosis resulting in end-stage renal disease. Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, α-actinin–4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing understanding of genes involved in the pathogenesis of focal segmental sclerosis, the vast majority of patients with this disease, even those with a familial linkage, lack a clear genetic diagnosis. Here, we tested whether combinations of genetic heterozygosity (bigenic heterozygosity) that alone do not result in clinical kidney disease could function together to enhance susceptibility to glomerular damage and FSGS. Combinations of Cd2ap heterozygosity and heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like glomerular damage. These genetic interactions were also reflected at a functional level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1. This demonstrates that bigenic heterozygosity can lead to FSGS and suggests that combined mutations in 2 or multiple podocyte genes may be a common etiology for glomerular disease.
beta-Amyloid Formation as a Potential Therapeutic Target for Alzheimer's Disease
Authors: B Cordell
Journal: The Annual Review of Pharmacology and Toxicology (1994)

As prolonged life expectancy has increased the proportion of the population that is elderly, Alzheimer's disease has emerged as a major health problem in the United States. Currently, 3 million Americans suffer from Alzheimer's disease. This number is expected to grow to greater than 10 million within the next decade. There is no remission in the progression of the disease, nor is there any truly effective pharmaceutical intervention. Hence, upon onset, the disease progresses inexorably towards increasing mental and physical incapacitation, followed by death. This process commonly lasts from two to twelve years. Presently, the financial burden from institutional care of demented Alzheimer'S disease patients is estimated at 40 billion dollars per year. Perhaps the greatest tragedy is the emotional burden to the afflicted individual and his or her family. Although the cause of Alzheimer's disease is unknown, recent molecular and biological research, in conjunction with classical neuropathological techniques, has contributed detailed insights into the pathogenesis of this disease. Particular attention has been devoted to the J3-amyloid plaque, which is the major histopathological hallmark of Alzheimer'S disease. Current evidence indicates that J3-amyloid deposition may play a central role in the pathogenesis of this disease, and recent findings have prompted
STUDIES ON THE CIRCULATION IN MAN
Authors: G. N. Stewart
Journal: The Journal of Experimental Medicine (1915)

The development of the collateral circulation after ligation of the innominate and right common carotid arteries for subclavian aneurysm was studied in two cases by measuring the rate of blood flow in the hand's from time to time. In a woman, sixty-eight years old, the flow in the right hand three weeks after the operation was two-sevenths of that in the left. Nineteen weeks after the operation the flow in the right hand was more than three-fourths of that in the left, although no pulse returned until long afterwards. In a man, twenty-five years old, the flow in the right hand eleven days after the operation was between one-fourth and one-fifth of that in the left. Seventeen days after the operation the flow in the right hand was nearly one-third of the flow in the left. Twenty-four days after the operation the flow in the right hand had increased to more than one-half of the left hand flow. Thirty-one days after the operation the flow in the right hand was three-fifths of that in the left, without return, as yet, of any pulsation. Before the operation the flow in the right hand was markedly greater than in the left, notwithstanding the small size of the right radial pulse as compared with the left. The explanation of this fact is discussed.
Stimulation of Mitochondrial Activity by p43 Overexpression Induces Human Dermal Fibroblast Transformation
Authors: Stéphanie Grandemange, Pascal Seyer, Angel Carazo, Philippe Bécuwe, Laurence Pessemesse, Muriel Busson, Cécile Marsac, Pascal Roger, François Casas, Gérard Cabello, Chantal Wrutniak-Cabello
Journal: Cancer Research (2005)

Abstract Mitochondrial dysfunctions are frequently reported in cancer cells, but their direct involvement in tumorigenesis remains unclear. To understand this relation, we stimulated mitochondrial activity by overexpression of the mitochondrial triiodothyronine receptor (p43) in human dermal fibroblasts. In all clones, this stimulation induced morphologic changes and cell fusion in myotube-like structures associated with the expression of several muscle-specific genes (Myf5, desmin, connectin, myosin, AchRα). In addition, these clones displayed all the in vivo and in vitro features of cell transformation. This phenotype was related to an increase in c-Jun and c-Fos expression and extinction of tumor suppressor gene expression (p53, p21WAF1, Rb3). Lastly, reactive oxygen species (ROS) production was increased in positive correlation to the stimulation of mitochondrial activity. The direct involvement of mitochondrial activity in this cell behavior was studied by adding chloramphenicol, an inhibitor of mitochondrial protein synthesis, to the culture medium. This inhibition resulted in partial restoration of the normal phenotype, with the loss of the ability to fuse, a strong decrease in muscle-specific gene expression, and potent inhibition of the transformed phenotype. However, expression of tumor suppressor genes was not restored. Similar results were obtained by using N-acetylcysteine, an inhibitor of ROS production. These data indicate that stimulation of mitochondrial activity in human dermal fibroblasts induces cell transformation through events involving ROS production.
Serum levels of Clara cell secretory protein, asthma, and lung function in the adult general population
Authors: Marta Rava, Lluisa Tares, Iris Lavi, Esther Barreiro, Jan-Paul Zock, Anna Ferrer, Nerea Muniozguren, Rachel Nadif, Lucia Cazzoletti, Francine Kauffmann, Josep M. Anto, Stefano Guerra
Journal: Journal of Allergy and Clinical Immunology (2013)
Cold urticaria in association with cholinergic urticaria
Authors: A.D. Ormerod, A. Kobza Black, M.W. Greaves
Journal: British Journal of Dermatology (1987)

Journal Article Cold urticaria in association with cholinergic urticaria Get access A.D. Ormerod, A.D. Ormerod Institute of Dermatology, St John's Hospital for Diseases of the Skin, London WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar A. Kobza Black, A. Kobza Black Institute of Dermatology, St John's Hospital for Diseases of the Skin, London WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar M.W. Greaves M.W. Greaves Institute of Dermatology, St John's Hospital for Diseases of the Skin, London WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue s32, 1 June 1987, Page 18, https://doi.org/10.1111/j.1365-2133.1987.tb11999.x Published: 01 June 1987
Developing a pictorial Epworth Sleepiness Scale
Authors: R. Ghiassi, K. Murphy, A. R. Cummin, M. R. Partridge
Journal: Thorax (2010)

<h3>Objective</h3> The Epworth Sleepiness Scale (ESS) was designed to be self-completed by the patient. However, it may not be understood by all, and unrecognised problems with literacy can impair the process. The ESS has been translated into a pictorial version for use in those with normal or diminished literacy skills. <h3>Methods</h3> An evaluation of the patients9 ability to self-complete the ESS was undertaken in sleep and non-sleep respiratory clinics. Errors or problems encountered were recorded on a standard questionnaire. With the aid of a medical artist, pictorial representations of the eight ESS questions were developed and the new pictorial ESS was offered to patients alongside the traditional ESS. The two scales were compared for agreement with a kappa statistic, and patients were asked to record a preference for either the written or the pictorial scale. <h3>Results</h3> Evaluation of the traditional ESS showed that 33.8% (27/80) of ESS-naive patients made errors and 22.5% (18/80) needed help completing the questionnaire. The translated pictorial ESS showed good agreement with the traditional ESS on most questions; median kappa score 0.63, IQR 0.04. Fifty-five per cent reported a preference for the pictorial scale compared with the standard written ESS. Despite the fact that errors were frequently made on the traditional ESS, 96.8% of participants in the second study reported both scales to be easy to complete. More people (75.6%) reported the pictorial ESS to be very easy, in comparison with (64.6%) the worded ESS questionnaire. <h3>Conclusion</h3> Errors are common when patients self-complete the traditional written ESS. Pictures with words have been shown to enhance the understanding and translation of medical information, and a pictorial translation of the ESS produces scores comparable with the traditional ESS and may be a suitable alternative for those with normal or diminished literacy.
The new sexual dimorphism.
Authors: N C Sharp
Journal: British Journal of Sports Medicine (1997)

<h3>Abstract</h3> <h3>Purpose</h3> Stuttering is characterized by intermittent speech disfluencies which are dramatically reduced when speakers synchronize their speech with a steady beat. The goal of this study was to characterize the neural underpinnings of this phenomenon using functional magnetic resonance imaging. <h3>Method</h3> Data were collected from 17 adults who stutter and 17 adults who do not stutter while they read sentences aloud either in a normal, self-paced fashion or paced by the beat of a series of isochronous tones (“rhythmic”). Task activation and task-based functional connectivity analyses were carried out to compare neural responses between speaking conditions and groups. <h3>Results</h3> Adults who stutter produced fewer disfluent trials in the rhythmic condition than in the normal condition. While adults who do not stutter had greater activation in the rhythmic condition compared to the normal condition in regions associated with speech planning, auditory feedback control, and timing perception, adults who stutter did not have any significant changes. However, adults who stutter demonstrated increased functional connectivity between bilateral inferior cerebellum and bilateral orbitofrontal cortex as well as increased connectivity among cerebellar regions during rhythmic speech as compared to normal speech. <h3>Conclusion</h3> Modulation of connectivity in the cerebellum and prefrontal cortex during rhythmic speech suggests that this fluency-inducing technique activates a compensatory timing system in the cerebellum and potentially modulates top-down motor control and attentional systems. These findings corroborate previous work associating the cerebellum with fluency in adults who stutter and indicate that the cerebellum may be targeted to enhance future therapeutic interventions.
Understanding HIV Latency: The Road to an HIV Cure
Authors: Matthew S. Dahabieh, Emilie Battivelli, Eric Verdin
Journal: Annual Review of Medicine (2015)

Treatment with antiretroviral therapy dramatically increases the survival of HIV-infected individuals. However, treatment has to be continued for life because it does not lead to the full eradication of infection. HIV persists in resting CD4 + T cells, and possibly other cell types, and can reemerge from these cells when therapy is interrupted. Here, we review molecular mechanisms that have been proposed to contribute to HIV latency, as well as the relative roles of cis- and trans-acting mechanisms. We also discuss existing and future therapeutic opportunities regarding HIV latency that might lead to a future cure for HIV infection.
Local Regulation of Arterial L-Type Calcium Channels by Reactive Oxygen Species
Authors: Gregory C. Amberg, Scott Earley, Stephanie A. Glapa
Journal: Circulation Research (2010)

Reactive oxygen species (ROS) are implicated in the development of cardiovascular disease, and oxidants are important signaling molecules in many cell types. Recent evidence suggests that localized subcellular compartmentalization of ROS generation is an important feature of ROS signaling. However, mechanisms that transduce localized subcellular changes in redox status to functionally relevant changes in cellular processes such as Ca(2+) influx are poorly understood.To test the hypothesis that ROS regulate L-type Ca(2+) channel activity in cerebral arterial smooth muscle.Using a total internal reflection fluorescence imaging-based approach, we found that highly localized subplasmalemmal generation of endogenous ROS preceded and colocalized with sites of enhanced L-type Ca(2+) channel sparklet activity in isolated cerebral arterial smooth muscle cells. Consistent with this observation and our hypothesis, exogenous ROS increased localized L-type Ca(2+) channel sparklet activity in isolated arterial myocytes via activation of protein kinase Cα and when applied to intact cerebral arterial segments, exogenous ROS increased arterial tone in an L-type Ca(2+) channel-dependent fashion. Furthermore, angiotensin II-dependent stimulation of local L-type Ca(2+) channel sparklet activity in isolated cells and contraction of intact arteries was abolished following inhibition of NADPH oxidase.Our data support a novel model of local oxidative regulation of Ca(2+) influx where vasoconstrictors coupled to NAPDH oxidase (eg, angiotensin II) induce discrete sites of ROS generation resulting in oxidative activation of adjacent protein kinase Cα molecules that in turn promote local sites of enhanced L-type Ca(2+) channel activity, resulting in increased Ca(2+) influx and contraction.
The kidney in liver transplantation.
Authors: D A Distant, T A Gonwa
Journal: Journal of the American Society of Nephrology (1993)

Renal dysfunction often complicates the course of liver transplant recipients. Preoperative renal dysfunction, including hepatorenal syndrome (HRS) may be present. Assessment of renal function in the pretransplant patient with end-stage liver disease is fraught with pitfalls. Direct measurement of GFR by a method other than creatinine clearance is recommended wherever possible. Preoperative renal biopsy should also be considered in those patients with renal dysfunction in whom the diagnosis of HRS is not definite. With the routine use of veno venous bypass, renal perfusion is maintained and intraoperative events generally do not play a significant role in the development of postoperative dysfunction. Postoperatively immunosuppressive medications such as CsA or FK506 account for most of the renal dysfunction that is observed. Other factors such as graft dysfunction, sepsis, and nephrotoxic drugs may also participate in renal impairment. The exact mechanism of cyclosporine or FK506 nephrotoxicity remains unknown. In liver transplant recipients, no convincing therapeutic strategies exist to combat nephrotoxicity other than dose reduction of immunosuppressive therapy. Patients with HRS can be successfully treated by liver transplantation with recovery of renal function and with patient survival rates comparable to recipients without HRS, despite increased morbidity.
Primary thrombophilia in Mexico. II. Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphism in thrombophilic Mexican mestizos
Authors: Guillermo J. Ruiz-Arg�elles, Javier Garc�s-Eisele, Virginia Reyes-N��ez, Francisco J. Ram�rez-Cisneros
Journal: American Journal of Hematology (2000)

We have shown that in Mexican mestizo patients with clinical features of primary thrombophilia, 39% have activated protein C resistance phenotype, 5% protein C deficiency, and 2% protein S deficiency. In the present study, in a group of 37 thrombophilic Mexicans and 50 normal controls, we assessed the factor V G1691A (Leiden), the prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms. Four patients were found to be heterozygous for factor V Leiden, 5 heterozygous for the prothrombin 20210, 16 heterozygous, and 6 homozygous for the MTHFR 677. There were four individuals with co-segregation of alleles: two heterozygotes for the factor V Leiden/prothrombin 20210, one heterozygote for prothrombin 20210/MTHFR 677, and one heterozygote for prothrombin 20210/homozygote for MTHFR 677. For factor V Leiden, prothrombin 20210, and MTHFR 677 mutations, the allele frequencies were respectively 1% (±0.2%, α = 0.05), <1% and 51% (±5%, α = 0.05), with calculated relative risks for thrombosis of 5.94 (P = 0.08), >7.66 (P < 0.05), and 0.44 (P NS), respectively. In Mexican mestizo thrombophilic patients, the low prevalence of the factor V Leiden mutation (10.8%) and the high prevalence of the prothrombin 20210 mutation (13.5%) contrast with those identified in Caucasian thrombophilic patients (21% and 6%, respectively; P < 0.01). On the other hand, the high prevalence of the MTHFR 677 mutation gene both in normal controls (78%) and thrombophilic patients (61%) does not support a role of this mutation in the thrombogenesis of Mexican mestizo patients. Am. J. Hematol. 66:28–31, 2001. © 2001 Wiley-Liss, Inc.
A MENTAL HYGIENE PROGRAM FOR THE MILITARY HOSPITAL
Authors: LOUIS S. LIPSCHUTZ, REBECCA ROSEN
Journal: American Journal of Psychiatry (1945)

1. A mental hygiene program for the psychiatrically unfit soldier returning directly to civilian life has been described. 2. This program employs group psychotherapy combined with personal interviews to: (a) present an essentially physiological etiology of psychoneuroses in terms of situational reaction to a specific,i. e., military, environment; (b) deliberately arouse guilt by a discussion of evasion of duties and responsibilities and guide the emotional forces so generated along the lines of ventilation of hostilities and aggressive drives and compensating for guilt and inferiority by full participation in the war effort on return to civilian status. 3. The psychoneuroses, particularly the anxiety and psychosomatic states responded well to this approach. 4. The pre-psychotic, the psychopaths and the mentally deficient were largely unaffected. 5. The social and economic effects of persisting guilt and inferiority when exposed to critical and stigmatizing community attitudes were described as: (a) resulting in the development of groups of chronically dissatisfied, insecure persons the easy prey of demagogues and pressure groups and therefore a focus of social instability; (b) the motivation for persisting disability in order to justify return to civilian status with consequent loss of social productivity and continued dependency at enormous economic cost. 6. The need for an aggressive program of public education to complement this approach was emphasized. The sympathetic response of representative public groups to such a program was noted.
Omalizumab decreases IgE production in patients with severe allergic asthma
Authors: Marisa Huebner, Stephanie Korn, Matthias Jung, Roland Buhl
Journal: European Respiratory Journal (2012)

A pharmacokinetic-pharmacodynamic model predicts that omalizumab reduces production of IgE 1. To test this hypothesis serum total-IgE concentrations were quantified in 64 patients with severe allergic asthma (mean±SEM, 46.2±13 yrs, 41 female, 81.6±15 kg, total IgE 397±189 IU/ml, FEV1 2.1±0.1 L or 64.7±2.4 % pred., eNO 51.2±7.4 ppb) treated with omalizumab (median 450 mg/month). Total serum IgE, asthma control (ACQ), lung function (FEV1) and exhaled nitric oxide (eNO) were evaluated at baseline (w0, n=64), after 16 weeks (w16, n=64) and after 52 weeks (w52, n= 24) of treatment.

50 patients responded to omalizumab treatment. Overall (n=64), after 16 weeks ACQ (w0 3.2± 0.16, w16 2.3±0.18; p<0.001), FEV1 (w16 2.3±0.12; p=0.01) and eNO (w16 40.1±5.4; p=0,027) improved significantly. Total IgE increased by 536±141 IU/ml (w16 984±215 IU/ml, p<0,001). Changes in total-IgE did not differ between responders and non-responders. After 52 weeks total IgE was 643±197 IU/ml, a decrease by 99±53 IU/ml vs. week 16 IgE levels, whereas ACQ, FEV1 and eNO remained stable. In this period total IgE serum concentrations decreased in 19 of 24 patients.

These results support the conclusion that long-term omalizumab treatment reduces IgE production. Further, total serum IgE should provide a means to monitor IgE production and guide individual treatment decisions.

1. Lowe PJ, Renard D. Omalizumab decreases IgE production in patients with allergic (IgE-mediated) asthma; PKPD analysis of a biomarker, total IgE. Br J Clin Pharmacol 2011; 72(2):306-320.