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PubMed1999

The role of therapeutic apheresis in the treatment of cancer: a review.

Immunosuppression is a hallmark of advanced malignancies in man. Over the past 40 years, many investigators have identified soluble immunosuppressive factors in blood, serum, ascitic fluid, and pleural fluid from cancers in man and other species. Suppressive factors have also been identified that are produced by tumors. The description of immunosuppressive factors in the blood of vertebrates who either have cancer or who are pregnant is significant, for only in pregnancy and cancer does a seemingly normal immune system tolerate immunogenic neoantigen. Tumor necrosis factors (TNFs) are known to be pleiotropic cytotoxic cytokines that are produced by macrophages and lymphocytes. These cells are thought to be suppressed in patients who have cancer or who are pregnant. Recently, elevated blood levels of soluble tumor necrosis factor receptors (sTNFRs) have been reported in the blood in a variety of cancers and pregnancy. In 1990, after our initial publication of the discovery of sTNFRs in the serum and low molecular weight ultrafiltrates of serum from a variety of cancer patients, others confirmed significant elevations of sTNFRs in cancer patients. This elevation was found to correlate with a poor prognosis. The biologic activity of proinflammatory cytokines as well as the suppressive role of their shed receptors is herein reviewed. Work with cancer patients using ultrapheresis to reduce these suppressive molecules by the authors and others is reviewed. Several recommendations are made for future directions.

Animals↗
PubMed1992

U1 snRNP targets an essential splicing factor, U2AF65, to the 3' splice site by a network of interactions spanning the exon.

A description of cellular factors that govern alternative splicing of pre-mRNA is largely incomplete. In the case of the rat preprotachykinin gene, splicing of the alternative exon E4 occurs by a poorly understood mechanism in which exon selection is under the positive control of U1 snRNP. Because the binding of U1 snRNP to the 5' splice site of E4 is coincident with the selection of the 3' splice site of E4, this mechanism would appear to involve interactions that bridge across the exon. In this work, a UV cross-linking strategy was used to identify possible RNA-protein interactions involved in the proposed exon-bridging model. Of particular interest is a prominent 61-kD protein, p61, that binds to the 3' splice site of E4 in a manner that is clearly facilitated by a downstream 5' splice site and U1 snRNP particles. The identity of p61 is the essential splicing factor U2AF65, on the basis of copurification and selective binding to polypyrimidine tracts. These results indicate a model in which exon selection is positively regulated by the communication of U1 snRNP and U2AF65. That is, a natural deficiency in binding U2AF65 to the 3' splice site that leads to exon skipping might be overcome by a mechanism in which U1 snRNP facilitates the binding of U2AF65 through a network of template-directed and exon-bridging interactions.

Base Sequence↗
PubMed2026

Hemotropic mono- and coinfections in Colombian ruminants: descriptive occurrence and host-related factors associated with coinfection in cattle.

Hemotropic pathogens such as Anaplasma, Babesia, Mycoplasma, and Trypanosoma are endemic to cattle and can cause coinfections, complicating disease dynamics and control. However, the host-related factors influencing these infections under tropical conditions remain poorly understood. This study aimed to investigate the occurrence of hemotropic monoinfections and coinfections in ruminants tested for hemotropic pathogens and to identify host-related factors associated with coinfection in cattle under field conditions in Colombia. A total of 104 animals were included: 91 cattle, 10 buffaloes, and 3 goats. Among the cattle, 34 (37.4%) exhibited monoinfections, 47 (51.6%) had coinfections, and 10 tested negative. In buffaloes, seven (70%) presented monoinfections, and two (20%) presented coinfections; in goats, one had a monoinfection, and one had a coinfection, most frequently involving Mycoplasma spp. The predominant coinfection patterns were Anaplasma&#x2009;+&#x2009;Mycoplasma and Mycoplasma&#x2009;+&#x2009;Trypanosoma, particularly in Bos indicus cattle. Bivariate and multivariable analyses revealed that breed was the strongest predictor of coinfection, with animals of less common breeds showing 93% lower odds (aOR&#x2009;=&#x2009;0.07; 95% CI: 0.02-0.30; p&#x2009;<&#x2009;0.001). Bos taurus individuals also tended toward lower odds of coinfection in the multivariable model, although this trend did not reach statistical significance. Our findings demonstrate a high frequency of hemotropic coinfections in cattle, particularly those involving Mycoplasma spp., and highlight the influence of host-related factors on infection dynamics. These results underscore the importance of integrating demographic and genetic information into surveillance and prevention strategies to improve the management of hemotropic infections in tropical livestock systems.

Animals↗
PubMed2001

Clinical description of encephalopathic syndromes and risk factors for their occurrence and outcome during melarsoprol treatment of human African trypanosomiasis.

Encephalopathies are the most feared complications of sleeping sickness treatment with melarsoprol. To investigate the existence of risk factors, the incidence of encephalopathic syndromes and the relationship between the development of different types of encephalopathies and the clinical outcome was studied in a clinical trial with 588 patients under treatment with melarsoprol. The 38 encephalopathy cases were classified into three types according to the leading clinical picture: coma type, convulsion type and psychotic reactions. Nine patients were attributed to the convulsion type, defined as a transient event of short duration with convulsions followed by a post-ictal phase, without signs of a generalized disease. None of these patients died from the reaction. Febrile reactions in the 48 h preceding the reaction were generally not observed in this group. Twenty-five patients were attributed to the coma type, which is a progredient coma lasting several days. Those patients often had signs of a generalized disease such as fever (84%), headache (72%) or bullous skin (8%) reactions. The risk of mortality was high in this group (52%). About 14/16 patients with encephalopathic syndrome of the coma type were infected with malaria. Patients with psychotic reactions or abnormal psychiatric behaviour (3/38) and one patient who died after alcohol intake were excluded from the analysis. The overall rate of encephalopathic syndromes in the cases analysed (n=34) was 5.8%, of which 38.2% died. We did not find any parameters of predictive value for the risk of developing an encephalopathic syndrome based on the symptoms and signs before treatment initiation. The appearance during treatment of febrile reactions (RR 11.5), headache (RR 2.5), bullous eruptions (RR 4.5) and systolic hypotension (RR 2.6) were associated with an increased risk for the occurrence of encephalopathic syndromes especially of the coma type.

Adult↗
PubMed1996

A low-Km 5'-nucleotidase from rat brain cytosolic fraction: purification, kinetic properties, and description of regulation by a novel factor that increases sensitivity to inhibition by ATP and ADP.

A readily soluble 5'-nucleotidase was purified 1,800-fold from rat brain 105,000-g supernatant. The enzyme showed similarity to the 5'-nucleotidase ectoenzyme of plasma membranes. It exhibited a low Km for AMP, which was preferred over IMP as substrate. It was inhibited by free ATP and ADP and by alpha,beta-methylene ADP. The enzyme appeared to be a glycoprotein on the basis of its interaction with concanavalin A. It contained a phosphatidylinositol moiety because treatment with phosphatidylinositol-specific phospholipase C increased its hydrophilicity. A single subunit of Mr = 54,300 +/- 800 was observed, which is appreciably smaller than published values for the 5'-nucleotidase ectoenzyme or for other low- Km "soluble" 5'-nucleotidases. The soluble 5'-nucleotidase showed an elution profile on AMP-Sepharose affinity chromatography or on Mono Q ion-exchange chromatography different from that of the brain ectoenzyme. Forty-two percent of the soluble 5'-nucleotidase in brain 105,000-g supernatant did not bind to a Mono Q ion-exchange column because of its interaction with a soluble factor. This factor could be removed by chromatography on concanavalin A-Sepharose. The factor had the novel property of increasing the sensitivity of the purified soluble 5'-nucleotidase toward the inhibitor ATP by 20-fold. This factor was also able to increase the inhibition of brain 5'-nucleotidase ectoenzyme by ATP.

5'-Nucleotidase↗
PubMed2005

A mathematical description of the functionality of correction factors used in allometry for predicting human drug clearance.

The functionality of the correction factors, maximum life-span potential (MLP), and brain weight (BrW) used in allometry is mathematically described. Correction by MLP or BrW is equivalent to a multiplication of some constants by the predicted values in humans from simple allometry, but they have no relationship to measured pharmacokinetic parameters in the animal species. The values of these constants (F(MLP) or F(BrW)) were calculated for some commonly used combinations of animal species. For all combinations of animal species, the value of F(BrW) is always greater than that of F(MLP) with a fold-increase of about 1.3 to 1.9. Different combinations of species give different values of F(BrW) and F(MLP). In addition, the role of correction factors (MLP and BrW) or the "rule of exponents" (ROE) was evaluated. An intrinsic defect in using correction factors or ROE was revealed; different study designs will produce significantly different prediction results. However, ROE may still serve as a useful practical approach in predicting human CL since it was derived from real observations and has been applied to many examples.

Animals↗
PubMed2006

Comments on "a mathematical description of the functionality of correction factors used in allometry for predicting human drug clearance".

In a recent paper, Tang and Mayersohn [(2005) Drug Metab Dispos 33:1294-1296] mathematically described the functionality of the correction factors (CFs), maximum life-span potential (MLP), and brain weight (BrW) used in allometric scaling for the prediction of human drug clearance. They found that there is an intrinsic defect in using correction factors because different combinations of species will produce different prediction results. Analysis with real examples reveals that different predicted clearance values observed with different combinations of animal species, with or without CFs, are not due to the intrinsic defect of the correction factors; rather, it is the effect of the species, observed clearance values in the species, and the range of the body weights. Even if one does not use the CF, the predicted clearance by the simple allometry will still vary by severalfold, depending on the species used in the scaling.

Animals↗
PubMed1995

A 'big five' scoring system for the item pool of the adjective check list.

The item pool of the Adjective Check List (ACL; Gough & Heilbrun, 1980) is widely used as a means of capturing the personal characteristics associated with various target groups (e.g., women vs. men, young adults vs. old adults). The purpose of this research was to develop a system for scoring the ACL items in terms of the five-factor model of personality. In Study 1, five groups of introductory psychology students served as judges, with each group of approximately 100 persons rating the 300 ACL items for one of the five factors. The ratings of each factor were highly reliable. When corrected for favorability, the intercorrelations among the five factors were quite low, as expected, except for the positive correlation of Openness and Extraversion. Good convergence was found between our ratings and the indicative and counterindicative items identified by John's (1989) graduate student judges. In Study 2, convergent validity was demonstrated between the five-factor scores obtained from self-descriptive ACLs and corresponding factor scores obtained from Costa and McCrae's NEO-PI-R and NEO-FFI instruments (Costa & McCrae, 1992). Data from earlier cross-cultural studies of gender and age stereotypes were rescored using the new ACL-FF system to illustrate its potential utility as a research tool.

Journal Article↗
PubMedDate not supplied

[Descriptive epidemiology of the vascular risk factors in Bañeres. Study group 'Bañeres Project'].

INTRODUCTION: Epidemiological studies of the risk factors of cerebrovascular disease are of great interest, particularly the identification of factors which may be modified. Previous studies carried out in the Alcoi region of Alicante province, showed a high prevalence of cerebrovascular disease. The town of Bañeres was therefore chosen for confirmation of this data and identification of the frequency of vascular risk factors. OBJECTIVE: To compare the group of patients with cerebrovascular disease with the remainder of the population interviewed. PATIENTS AND METHODS: In a door-to-door study in Bañeres 1,832 people were interviewed as part of the Bañeres Project. The population aged over 45 years was interviewed and filled in a questionnaire for diagnosis of transient ischemic accidents. RESULTS: Arterial hypertension: estimated prevalence 500/1,000 inhabitants, relative risk 3.24; diabetes mellitus: estimated prevalence 195/1,000, relative risk 2.18; coronary artery disease: estimated prevalence 58/1,000, relative risk 1.88; peptic ulcer: estimated prevalence 75/1,000, relative risk 1.23; smoking: estimated prevalence 110/1,000, relative risk 0.46; complete arrhythmia: prevalence 73/1,000, relative risk 5.23. Family histories of cerebrovascular accident, arterial hypertension, diabetes and coronary artery disease were not significant. CONCLUSIONS: Arterial hypertension, diabetes mellitus and arrhythmia were significantly more prevalent amongst patients with vascular disease in our setting. We found no association with the other risk factors analyzed.

Aged↗
PubMed1996

[The epidemiology and genetics of asthma. I. Descriptive epidemiology and analysis of environmental factors].

Asthma is regarded as a disease with a complex interaction between genetic and environmental factors. Since the end of the 1970s and during the 80s the world has seen an increase in the prevalence, morbidity and mortality linked to asthma. The rapidity of progress of this phenomenon means that it cannot be explained only by modification of genetic factors and stresses the preponderance of exogenous factors. The purpose of this review is to examine the epidemiological knowledge of these environmental factors and of the genetic factors in asthma in order to underline how these genetic and exogenous factors interact and modulate the occurrence of the asthmatic disease. In the first part of this general review we will discuss the epidemiology of asthma in terms of prevalence, incidence, mortality, cost and socio-professional and scholastic repercussions and will underline for each environmental factor its causal role and/or exacerbation in asthma as well as its contribution in the increased prevalence and severity of asthma. In the second part of this general view we touch on the epidemiological knowledge of the genetics of asthma and of atopy.

Absenteeism↗
PubMed2003

Factors in duration of anxiolytic, sedative, and hypnotic drug use in the elderly.

At least 2 decades of descriptive research on factors associated with psychotropic drug use by the elderly in the community has failed to yield convergent results. The authors posited that duration of use may have been confounding results of previous studies, since variables influencing initial use may not be those influencing long-term use. They conducted a secondary analysis of the elderly respondents in the cross-sectional 1998 Quebec Health Survey (n = 3,012). Results clearly show that factors associated with ASH use vary with duration of use. Apart from depression, medical and mental health factors significant for short-term use are not associated with long-term use. The only factors found that explain long-term but not short-term use were gender (female) and health perception (less than positive). These findings suggest that over the long term it is unlikely that mental health therapeutic benefits explain ASH use. The authors hypothesize that drug dependency could play a role in long-term use. They therefore encourage community health nurses to implement withdrawal programs in order to reduce harmful long-term consumption.

Aged↗
PubMed1992

Factors affecting neural stimulation with magnetic fields.

High amplitude magnetic field pulses produced by coils external to the body have been used for medical diagnosis since the mid-1980s to stimulate motor neurons in the brain cortex and peripheral nerves. While successful applications have since blossomed, it has only been during the last three years that quantitative dosimetric data have become available. The factors affecting neural stimulation can be divided into three categories broadly related to the characteristics of (i) the stimulus, (ii) the neuron, and (iii) the induced electric field as related to the configuration of the stimulating coil. The stimulus, in the case of magnetic field stimulation, has the form of an exponentially decaying pulse with a small overshoot of the opposite polarity. Physical and electrical properties of a neuron affect its electrical stimulation. Dosimetric considerations are limited to the linear model describing the threshold phenomena, where passive electrical properties and the cable model provide a reasonable approximation of neuron behavior. The electromagnetic variable responsible for stimulation is the spatial derivative of the induced electric field along the neuron axis. This paper examines the factors involved in eliciting threshold excitation of motor neurons by magnetic fields. The description of various factors is largely based on published data except for the analysis of the electromagnetic stimuli induced by various coils.

Animals↗