articles+ search results

LOW-fat diet and BLOOD cholesterol

Examines the effect of dietary cholesterol on plasma cholesterol concentration in subjects following low fat diet in Great Britain. Ratio of polyunsaturated to saturated fatty acids; Comparison of the cholesterol concentration among subjects; Importance of dietary cholesterol for the reduction of saturated fats.

An automated method for measuring beta-hydroxybutyrate was adapted to the Ciba-Corning 550 Express trade mark random access analyzer. The assay was based on a kinetic reaction utilizing hydroxybutyrate-dehydrogenase. Beta-hydroxybutyrate concentration (mmol/L) was calculated ratiometrically using a 1.0 mmol/l standard. Canine serum, plasma, and urine were used without prior deproteinization and only a 30-microliter sample was required. The method demonstrated good linearity between 0 to 2 mmol/l of beta-hydroxybutyrate. Analytical recovery (accuracy) within these concentrations ranged from 85.8 to 113.3%. Both within-run and day-to-day precision were determined, as was specificity of the assay in the presence of a variety of interfering substances. The automated assay was rapid and economical, with reagent stability maintained for at least 2 weeks at 4 degrees C. This assay can readily be applied toward the assessment of ketoacidosis in dogs, and with further validation, other species.

MEDICINE, FETAL tissue research, POPULATION & the environment, FETAL death, and POLITICAL science

Presents global developments on the political aspects of medicine as of March 1992. Progress on fetal tissue research and transplants in Australia, Europe, and the United States; Increase in human population; Disposal of fetuses and fetus remains.

ARCHAEOLOGICAL excavations, ARCHAEOLOGICAL surveying, ARCHAEOLOGY, INTERMENT, and IRON Age

Geophysical survey and excavation have demonstrated that iron age settlement features and early Anglo-Saxon burials discovered during road construction in 1983 were part o[ an extensive multi-period site, now a Scheduled Ancient Monument. This paper presents the results of the archaeological investigations. The bulk of the report is concerned with the early Anglo-Saxon burials, which included a grave containing a balance, weights and runic inscription. The evidence for late mesolithic, neolithic -- early bronze age, iron age and post-medieval activity is also discussed, and the site is considered in its regional and wider context. [ABSTRACT FROM AUTHOR]

BEER, INTERNATIONAL economic relations, and INTERNATIONAL trade

Demonstrates how United States and Canadian controls on the alcohol market affect public health. US-Canadian alcohol control; Public health implications; How the trade agreements (GATT, FTA, NAFTA) work; Trade disputes since 1985; The larger meaning of the disputes; Chronology of the US-Canada beer dispute; Glossary; Summary.

Adaptation, Psychological, Adult, Chronic Disease, Factor Analysis, Statistical, Female, Humans, Male, Regression Analysis, Social Support, Socioeconomic Factors, Surveys and Questionnaires, Life Change Events, Pain psychology, and Quality of Life

Cognitive appraisal processes or the meaning a person gives a stressful event are believed to mediate an individual's reaction to an event and, as such, have been demonstrated to explain adjustment to illness. The purpose of this paper is to test this cognitive as well as other social and illness variables to explain the variance in a person's adjustment to chronic pain. Two hundred and twenty-two patients, who were randomly selected from an original sample of referrals to a chronic pain specialty clinic, completed a questionnaire by telephone interview or mail. The questionnaire consisted of psychosocial scales (PAIS-SR; Social Support) and cognitions including the Meaning of Illness Questionnaire (MIQ). Fifty-six percent of the sample had poor psychosocial adjustment to their pain problem. Seventy percent of the variance in adjustment was explained by social and cognitive variables which corroborates their importance. The MIQ 5-factor structure was supported and provides credible evidence of the role of cognitions in differentiating between the poor and well adjusted.

ALCOHOL drinking

In a national sample of 11 634 Canadians aged 15 years and above, risk curves for harm to six life-areas from one's own drinking and for assault by another drinker rose steadily with the respondent's volume of alcohol consumption. While drinking five or more drinks on an occasion at least once a month substantially raised the risk at a given volume of drinking, the risk rose with volume even among those not regularly drinking five or more drinks. These relationships remained in logistic regressions which controlled for gender, age and educational level. Younger respondents, those without higher education and men reported more harm for a given level of their own drinking although differences by gender disappeared above one-third of one drink per day. Three sets of guidelines for low-risk drinking-two from Canada, and one generally used in Britain-were compared in terms of the proportions of respondents reporting harm from their own drinking among those who had kept within the guideline in the previous 7 days' drinking. More restrictiveness in the guidelines was associated with substantial reductions in reported drinking-related harm. [ABSTRACT FROM AUTHOR]

TUBERCULOSIS prevention, MEDICAL care of HIV-positive persons, ISONIAZID, PTERIDINES, and DRUG efficacy

Studies the effectiveness of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1 positive individuals. Methods for comparing efficacy of the chemoprophylaxis regimens; Findings; Interpretation. INSET: Disease categories.

PERSONALITY, ANGER, CITY traffic, AFRICAN Americans, AUTOMOBILE drivers, ATTITUDE (Psychology), and PSYCHOLOGICAL burnout

This study evaluates the psychosocial correlates of anger-related traits. Participants include New York City traffic enforcement agents (TEAs), who issue summonses for vehicular and parking violations and are frequently confronted by angry motorists. This sample of TEAs is 53% African American and 57% female. Participants completed surveys at 2 points, 4 months apart, which measured attitudinal, affective, and expressive components of hostility and anger, as well as dimensions of workplace psychosocial response. Results indicate that trait anger-in was positively associated with frequency of conflict, anger intensity, and burnout in cross-sectional analyses; and positively associated with frequency of conflict in prospective analyses. Trait anger was positively associated with an increase in burnout over a 4-month period. These findings provide support for the transactional model of hostility and health and have implications for worksite interventions promoting cardiovascular health. [ABSTRACT FROM AUTHOR]

COMMUNITY health services, NATIONAL health insurance, and MEDICAL care

A series of 12 studies (five historic cohort and seven randomized trials) examined clients in community settings in Southern Ontario suffering from a variety of chronic physical and mental health conditions. These studies are appraised using a framework for evaluating possible outcomes of economic evaluation. In the 12 studies, sample composition and size varied. Each study was designed to quantify the well-being outcomes and expenditures associated with different community-based approaches to care provided in the context of a system of national health insurance. As a collective, these studies represent increasing methodological rigour. Multiple-perspective client well-being outcome measures were used. In two studies, caregiver burden also was analysed. A common approach to quantification and evaluation of expenditures for service consumption was used in all 12 studies. The nature of community-based health services (health vs. disease care orientation) was found to have direct and measurable impact on total expenditures for health service utilization and client well-being outcomes. In most cases, a recurring pattern of equal or better client outcomes, yet lower expenditures for use of community based health services, was associated with well-integrated health oriented services. Integrated services aimed at factors which determine health are superior when compared to individual, fragmented, disease oriented, and focused approaches to care. The main lessons from the 12 studies are that it is as or more effective and as or less expensive to offer complete, proactive, community health services to persons living with chronic circumstance than to provide focused, on-demand, piecemeal services. Complete services would have a psychosocial and mental health focus included with the physical care approach. Furthermore, people with coexisting risk factors (age, living arrangements, mental distress and problem-solving ability) are the ones who most benefit at lower expense... [ABSTRACT FROM AUTHOR]

PERIODONTAL disease and KERATOSIS

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7-9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between DllS4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers. [ABSTRACT FROM AUTHOR]

SUBSTANCE abuse prevention, ETHNICITY, MEDICAL communication, ETHNIC groups, PATHOLOGICAL psychology, and SOCIAL psychology

The rationale for targeted and tailored substance use prevention programs derives from essentially three observations: 1) differences in substance use prevalence rates across racial/ethnic groups; 2) differences in the prevalence of the risk factors for substance use across racial/ethnic groups; and 3) differences in the predictors of substance use across groups. This article provides a model for understanding cultural sensitivity as it pertains to substance use prevention. Cultural sensitivity is defined by two dimensions, surface and deep structure. Surface structure involves matching intervention materials and messages to observable, “superficial” characteristics of a target population. This may involve using people, places, language, product brands, music, food, locations, and clothing familiar to, and preferred by, the target audience. Surface structure refers to how well interventions fit within a specific culture. Deep structure involves incorporating the cultural, social, historical, environmental, and psychologic forces that influence the target health behavior in the proposed target population. For example, peer influences may exert a greater influence on substance use initiation among White and Hispanic than among African American youth, while parental influences may be stronger among African Americans. Whereas surface structure generally increases the "receptivity" or "acceptance" of messages, deep structure conveys salience. Techniques for developing culturally sensitive interventions, borrowed from social marketing and health communication theory, are described. © 2000 John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

Adolescent, Adult, Age of Onset, Alleles, Child, Disease Progression, Female, Haplotypes genetics, Heterozygote, Humans, Male, Middle Aged, Molecular Sequence Data, Multiple Sclerosis pathology, Phenotype, Polymorphism, Single Nucleotide genetics, Probability, Survival Analysis, Apolipoproteins E genetics, Genetic Predisposition to Disease, Multiple Sclerosis genetics, Multiple Sclerosis physiopathology, and Polymorphism, Genetic genetics

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, with a complex etiology that includes a strong genetic component. The contribution of the major histocompatibility complex (MHC) has been established in numerous genetic linkage and association studies. In addition to the MHC, the chromosome 19q13 region surrounding the apolipoprotein E (APOE) gene has shown consistent evidence of involvement in MS when family-based analyses were conducted. Furthermore, several clinical reports have suggested that the APOE-4 allele may be associated with more-severe disease and faster progression of disability. To thoroughly examine the role of APOE in MS, we genotyped its functional alleles, as well as seven single-nucleotide polymorphisms (SNPs) located primarily within 13 kb of APOE, in a data set of 398 families. Using family-based association analysis, we found statistically significant evidence that an SNP haplotype near APOE is associated with MS susceptibility (P=.005). An analysis of disease progression in 614 patients with MS from 379 families indicated that APOE-4 carriers are more likely to be affected with severe disease (P=.03), whereas a higher proportion of APOE-2 carriers exhibit a mild disease course (P=.02).

Animals, Carcinogens, Environmental toxicity, Environmental Monitoring, Gasoline toxicity, Mollusca, Petroleum toxicity, and Polycyclic Aromatic Hydrocarbons toxicity

Fish and shellfish are exposed to a wide range of polycyclic aromatic hydrocarbons (PAH) following oil spills at sea, and can become contaminated as a result. Finfish have a more effective mixed-function oxidase enzyme system than shellfish, and are therefore able to metabolise and excrete PAH more effectively than the invertebrates. Thus, contamination by high-molecular weight PAH, including those with carcinogenic potential and so of concern with regard to human consumers, is therefore usually observed in shellfish, and particularly in bivalve molluscs. Oil spills are not the sole source of PAH, however, as parent compounds are also generated by a wide range of combustion processes. In this paper, consideration is given to monitoring data gathered following recent oil spills (both of crude oil and diesel fuel), alongside data from other studies. These include studies conducted around a former gasworks site and downstream of an aluminium smelter in the UK, and from mussel monitoring studies undertaken in the UK and the USA (including the Exxon Valdez oil spill and the National Status and Trends programme), and in other countries in Europe. For comparative purposes the PAH concentrations are summed and also expressed as benzo[a]pyrene equivalents, their relative concentrations being weighted in relation to the carcinogenic potential of individual PAH compounds using toxic equivalency factors (TEF). Our aim was to assess the utility of this approach in fishery resource monitoring and control following oil spills. Certainly this approach seems useful from the data assessed in this study. and the relative ranking of the various studies seems to reflect the relative degree of concern for human consumers due to the differing contamination sources. As a simple tool for control purposes it is equally applicable to PAH derived from oil spills, and from industrial and combustion sources.

Animals, Dose-Response Relationship, Drug, Drug Administration Schedule, Endothelin Receptor Antagonists, Endothelium, Vascular physiology, Enzyme Inhibitors pharmacology, Female, In Vitro Techniques, Infusion Pumps, Implantable, Nitric Oxide Synthase antagonists inhibitors, Peptides, Cyclic pharmacology, Pregnancy, Rats, Rats, Long-Evans, Receptor, Endothelin B, Vascular Patency drug effects, Vasoconstrictor Agents pharmacology, Vasodilator Agents pharmacology, Vasomotor System physiology, Arteries drug effects, Arteries physiology, Kidney blood supply, Relaxin pharmacology, and Vasomotor System drug effects

Administration of the ovarian hormone relaxin to nonpregnant rats vasodilates the renal circulation comparable to pregnancy. This vasodilation is mediated by endothelin (ET), the ET(B) receptor, and nitric oxide. Furthermore, endogenous relaxin mediates the renal vasodilation and hyperfiltration that occur during gestation. The goal of this study was to investigate whether myogenic reactivity of small renal and mesenteric arteries is reduced in relaxin-treated rats comparable to the pregnant condition. Relaxin or vehicle was administered to virgin female Long-Evans rats for 5 days at 4 microg/h, thereby producing midgestational blood levels of the hormone. The myogenic responses of small renal arteries (200-300 microm in diameter) isolated from these animals were evaluated in an isobaric arteriograph system. Myogenic reactivity was significantly reduced in the small renal arteries from relaxin-treated compared with vehicle-treated rats. The reduced myogenic responses were mediated by the ET(B) receptor and nitric oxide since the selective ET(B) receptor antagonist RES-701-1 and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester restored myogenic reactivity to virgin levels. The influence of relaxin was not limited to the renal circulation because myogenic reactivity was also reduced in small mesenteric arteries isolated from relaxin-treated rats. Thus relaxin administration to nonpregnant rats mimics pregnancy, insofar as myogenic reactivity of small renal and mesenteric arteries is reduced in both conditions.

Animals, Antithrombin III metabolism, Binding Sites, Brain Ischemia blood, Cattle, DNA Mutational Analysis, Factor Xa Inhibitors, Family Health, Genetic Variation, Humans, Hypercholesterolemia blood, Male, Middle Aged, Mutation, Missense, Protein Binding genetics, Antithrombin III chemistry, Antithrombin III genetics, and Heparin metabolism

Here we report the finding of a new natural antithrombin mutation that confirms the critical contribution of lysine 114 to the binding of the core heparin pentasaccharide, with the replacement of lysine 114 by glutamate causing a complete loss in affinity. The variant was identified in a father and son, the father having been investigated for an episode of cerebral ischaemia associated with hypercholesterolaemia. The variant forms SDS-stable complexes with activated factor X (fXa) and its thermal stability and rate of factor Xa inhibition in the absence of heparin are identical to those of normal antithrombin. Normal antithrombin binds to the high affinity heparin pentasaccharide with a Kd of 1nM, as detected by a 45% change in intrinsic fluorescence, resulting in a 230-fold increase in rate of factor Xa inhibition. However, no change in fluorescence was detected for the variant when titrated with heparin or the heparin pentasaccharide, nor was there detectable activation towards factor Xa, indicating a complete loss of heparin binding.

CONDENSATION, PYRYLIUM compounds, and CARBANIONS

The condensation reaction between γ-unsubstituted pyrylium salts and carbanions of Fischer-type carbene complexes allowed the synthesis of new γ-methylenepyran carbene complexes. NMR data, single crystal X-ray analysis, and DFT calculations suggest that these complexes have a partial pyrylium character due to the π electron-accepting ability of the carbenic fragment and to the electron-releasing properties of the methylenepyran part. [Copyright &y& Elsevier]

Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 6, Chromosomes, Human, Pair 7, Genetic Heterogeneity, HLA-DR2 Antigen genetics, Humans, Lod Score, Multiple Sclerosis etiology, Genetic Linkage, Genetic Predisposition to Disease, and Multiple Sclerosis genetics

Multiple sclerosis (MS) is a common and frequently disabling autoimmune disorder mediated by autoaggressive T cells and autoantibodies that target central nervous system myelin. While numerous studies have demonstrated a strong genetic component to MS, it has been difficult to identify the specific genes involved. Several genomic screens have been undertaken to locate such genes, but have not provided consistent gene localization, except for the MHC on chromosome 6p21 and a locus on chromosome 19q13. To determine which of the original genomic locations presented in the US genome screen could be replicated, a more detailed analysis of additional families was performed. The results, derived from a population of 266 affected individuals belonging to 98 multiplex families, continue to support linkage to chromosomes 6p21, 6q27, and 19q13 with LOD scores>3.0, and suggest that regions on chromosomes 12q23-24 and 16p13 may also harbor susceptibility loci for MS. Analysis taking into account the known HLA-DR2 association identified two additional potential linkage regions on chromosomes 7q21-22 and 13q33-34. These regions can now be targeted for detailed study to identify the underlying MS susceptibility genes.

Consultants, Humans, Librarians, Personnel Staffing and Scheduling standards, Societies, Workforce, Information Management standards, Libraries, Hospital standards, Library Services standards, and Professional Role

The Medical Library Association's "Standards for Hospital Libraries 2002" have been developed as a guide for hospital administrators, librarians, and accrediting bodies to ensure that hospitals have the resources and services to effectively meet their needs for knowledge-based information. Specific requirements for knowledge-based information include that the library be a separate department with its own budget. Knowledge-based information in the library should be directed by a qualified librarian who functions as a department head and is a member of the Academy of Health Information Professionals. The standards define the role of the medical librarian and the links between knowledge-based information and other functions such as patient care, patient education, performance improvement, and education. In addition, the standards address the development and implementation of the knowledge-based information needs assessment and plans, the promotion and publicity of the knowledge-based information services, and the physical space and staffing requirements. The role, qualifications, and functions of a hospital library consultant are outlined. The health sciences library is positioned to play a key role in the hospital. The increasing use of the Internet and new information technologies by medical, nursing, and allied health staffs; patients; and the community require new strategies, strategic planning, allocation of adequate resources, and selection and evaluation of appropriate information resources and technologies. The Hospital Library Standards Committee has developed this document as a guideline to be used in facing these challenges.

LETTERS to the editor, MEDICAL personnel, CLINICAL medicine, and PHYSICIANS' correspondence

Presents letters to the editor and correspondence between medical practitioners as of November 16, 2002. Undisclosed payments in research; Use of sildenafil for so-called blue babies; Making the best of health advocates and interpreters; Homosexual-related legislation and suicidal intent among sexual minority groups; Iron deficiency in women's health; Others.

Air Pollutants analysis, Aircraft, Humans, Musculoskeletal Diseases etiology, Musculoskeletal Diseases psychology, New York City, Occupational Diseases psychology, Occupational Health, Pilot Projects, Respiratory Tract Diseases psychology, Air Pollutants adverse effects, Occupational Diseases etiology, Occupational Exposure adverse effects, Rescue Work, Respiratory Tract Diseases etiology, and Terrorism

Aspergillus genetics, Aspergillus growth development, Blotting, Northern, Blotting, Southern, Fermentation, Heme metabolism, Mitosporic Fungi genetics, Peroxidase metabolism, Plasmids, Promoter Regions, Genetic, Aspergillus enzymology, Biotechnology methods, Mitosporic Fungi enzymology, and Peroxidase genetics

The heterologous production of Arthromyces ramosus peroxidase (ARP) was analysed in the filamentous fungus Aspergillus awamori under control of the inducible endoxylanase promoter. Secretion of active ARP was achieved up to 800 mg l(-1) in shake flask cultures. Western blot analysis showed that an rARP product of the correct molecular weight was produced. In contrast to several other studies about heterologous production of heme containing peroxidases, our results suggest that in A. awamori no heme limitation exists during overproduction of ARP.

Apoptosis drug effects, Butyrates pharmacology, Caco-2 Cells, Carcinoma drug therapy, Carcinoma metabolism, Carcinoma physiopathology, Caspase 3, Caspases drug effects, Caspases metabolism, Cell Adhesion drug effects, Cell Differentiation drug effects, Colonic Neoplasms drug therapy, Colonic Neoplasms metabolism, Colonic Neoplasms physiopathology, Down-Regulation drug effects, Down-Regulation physiology, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Humans, Integrin beta1 drug effects, Integrin beta1 metabolism, Integrins drug effects, Intestinal Mucosa drug effects, NF-kappa B drug effects, NF-kappa B metabolism, Phosphatidylinositol 3-Kinases drug effects, Phosphatidylinositol 3-Kinases metabolism, Phosphorylation drug effects, Protein-Tyrosine Kinases drug effects, Protein-Tyrosine Kinases metabolism, Proto-Oncogene Proteins drug effects, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-bcl-2 drug effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Signal Transduction drug effects, Signal Transduction physiology, Sucrase drug effects, Sucrase metabolism, Apoptosis physiology, Cell Adhesion physiology, Cell Differentiation physiology, Integrins metabolism, Intestinal Mucosa metabolism, and Protein Serine-Threonine Kinases

We previously reported that the enterocytic differentiation of human colonic Caco-2 cells correlated with alterations in integrin signaling. We now investigated whether differentiation and apoptosis of Caco-2 cells induced by the short-chain fatty acid butyrate (NaBT) was associated with alterations in the integrin-mediated signaling pathway with special interest in the expression and activity of focal adhesion kinase (FAK), of the downstream phosphatidylinositol 3'-kinase (PI 3-kinase)-Akt pathway and in the role of the nuclear factor kappaB (NF-kappaB). NaBT increased the level of sucrase. It induced apoptosis as shown by: (1) decreased Bcl-2 and Bcl-X(L) proteins and increased Bax protein; (2) activation of caspase-3; and (3) increased shedding of apoptotic cells in the medium. This effect was associated with defective integrin-mediated signaling as shown by: (1) down-regulation of beta1 integrin expression; 2) decreased FAK expression and tyrosine phosphorylation; (3) concerted alterations in cytoskeletal and structural focal adhesions proteins (talin, ezrin); and (4) decreased FAK ability to associate with PI 3-kinase. However, in Caco-2 cells, beta1-mediated signaling failed to be activated downstream of FAK and PI 3-kinase at the level of Akt. Transfection studies show that NaBT treatment of Caco-2 cells promoted a significant activation of the NF-kappaB which was probably involved in the NaBT-induced apoptosis. Our results indicate that the prodifferentiating agent NaBT induced apoptosis of Caco-2 cells probably through NF-kappaB activation together with a defective beta1 integrin-FAK-PI 3-kinase pathways signaling.

CELL differentiation, APOPTOSIS, FATTY acids, and PROTEINS

We previously reported that the enterocytic differentiation of human colonic Caco-2 cells correlated with alterations in integrin signaling. We now investigated whether differentiation and apoptosis of Caco-2 cells induced by the short-chain fatty acid butyrate (NaBT) was associated with alterations in the integrin-mediated signaling pathway with special interest in the expression and activity of focal adhesion kinase (FAK), of the downstream phosphatidylinositol 3'-kinase (PI 3-kinase)Akt pathway and in the role of the nuclear factor κB (NF-κB). NaBT increased the level of sucrase. It induced apoptosis as shown by: (1) decreased Bcl-2 and Bcl-XL proteins and increased Bax protein; (2) activation of caspase-3; and (3) increased shedding of apoptotic cells in the medium. This effect was associated with defective integrin-mediated signaling as shown by: (1) down-regulation of β1 integrin expression; 2) decreased FAK expression and tyrosine phosphorylation; (3) concerted alterations in cytoskeletal and structural focal adhesions proteins (talin, ezrin); and (4) decreased FAK ability to associate with PI 3-kinase. However, in Caco-2 cells, β1-mediated signaling failed to be activated downstream of FAK and PI 3-kinase at the level of Akt. Transfection studies show that NaBT treatment of Caco-2 cells promoted a significant activation of the NF-κB which was probably involved in the NaBT-induced apoptosis. Our results indicate that the prodifferentiating agent NaBT induced apoptosis of Caco-2 cells probably through NF-κB activation together with a defective β1 integrin-FAK-PI 3-kinase pathways signaling. J. Cell. Physiol. 197: 336347, 2003© 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Action Potentials physiology, Animals, Cells, Cultured, Cochlear Nerve physiology, Culture Techniques, Electric Stimulation methods, Immunohistochemistry, Kv1.1 Potassium Channel, Mice, Mice, Inbred CBA, Neurons classification, Neurons metabolism, Patch-Clamp Techniques, Potassium Channels biosynthesis, Protein Subunits biosynthesis, Reaction Time physiology, Neurons physiology, Potassium Channels, Voltage-Gated, and Spiral Ganglion cytology

Type I and type II spiral ganglion neurons convey auditory information from the sensory receptors in the cochlea to the CNS. The numerous type I neurons have been extensively characterized, but the small population of type II neurons with their unmyelinated axons are undetectable with most recording methods. Despite the paucity of information about the type II neurons, it is clear that they must have a significant role in sound processing because they innervate the large number of outer hair cells that are critical for maintaining normal responses to stimuli. To elucidate the function of type II neurons, we have developed an approach for studying their electrophysiological features in vitro. Type II neurons obtained from postnatal day 6-7 mice displayed distinctly different firing properties than type I neurons. They showed slower accommodation, lower action potential thresholds, and more prolonged responses to depolarizing current injection than the type I neurons. These differences were most evident in neurons from the basal, high-frequency region of the cochlea. The basal type I neurons displayed uniformly fast firing features, whereas the basal type II neurons showed particularly slow accommodation and responses to depolarization. Interestingly, neurons from the apical, low-frequency region of the cochlea showed the opposite trend. These data suggest that the type I and type II neurons have specialized electrophysiological characteristics tailored to their different roles in auditory signal processing. In particular, the type II neuron properties are consistent with cells in other sensory systems that receive convergent synaptic input for high-sensitivity stimulus detection.

Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 3, Cooperative Behavior, France, Genetic Predisposition to Disease, HLA-DR Antigens genetics, HLA-DR Serological Subtypes, Humans, United States, Genetic Linkage genetics, and Multiple Sclerosis genetics

Multiple sclerosis (MS) is a demyelinating autoimmune disease with a strong yet complex genetic component. To date only the HLA-DR locus, and specifically the HLA-DR15 allele, has been identified and confirmed as influencing the risk of developing MS. Genomic screens on several datasets have been performed and have identified several chromosomal regions with interesting results, but none have yet been confirmed. We tested seven of the most-promising regions (on chromosomes 1p, 2p, 3p, 3q, 5q, 19q, and Xp) identified from several genomic screens in a dataset of 98 multiplex MS families from the United States and 90 multiplex MS families from France. The results did not confirm linkage to 2p, 3q, 5q, or Xp in the overall dataset, or in subsets defined by geographic origin or HLA-DR15 status. Regions on 1p34, 3p14, and 19q13 produced lod scores >0.90 in at least one subset of the data, suggesting that these regions should be examined in more detail.

HABITAT selection, GLOBAL Positioning System, HABITATS, VEGETATION & climate, RADIO telemetry, and ANIMAL radio tracking

Journal of Applied Ecology (2004) 41, 201–212 [ABSTRACT FROM AUTHOR]

Anxiety Disorders physiopathology, Brain physiopathology, Humans, Obsessive-Compulsive Disorder epidemiology, Panic Disorder epidemiology, Phobic Disorders epidemiology, Schizophrenia physiopathology, Stress Disorders, Post-Traumatic epidemiology, Anxiety Disorders epidemiology, and Schizophrenia epidemiology

Anxiety symptoms and disorders have long been described in schizophrenia. This article reviews the epidemiology, phenomenology, and neurobiologic underpinnings of comorbid anxiety symptoms and disorders in schizophrenia. Recent literature was obtained by Medline searches using key words relating to schizophrenia and anxiety symptoms or disorders. There is some evidence that anxiety may be a core symptom dimension in schizophrenia, although further work is required. There is evidence that comorbid obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social anxiety disorder are all more common than expected by chance in schizophrenia, although additional work is needed to determine the mechanisms that underlie these associations and their clinical implications. In the interim, however, the data emphasize the importance of assessing and treating comorbid anxiety symptoms and disorders in schizophrenia.

Genetic Linkage, Genetic Markers, Genetic Predisposition to Disease, Humans, Lod Score, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 9, Cleft Lip genetics, and Cleft Palate genetics

Isolated or nonsyndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. A 10-cM genome scan of 388 extended multiplex families with CL/P from seven diverse populations (2,551 genotyped individuals) revealed CL/P genes in six chromosomal regions, including a novel region at 9q21 (heterogeneity LOD score [HLOD]=6.6). In addition, meta-analyses with the addition of results from 186 more families (six populations; 1,033 genotyped individuals) showed genomewide significance for 10 more regions, including another novel region at 2q32-35 (P=.0004). These are the first genomewide significant linkage results ever reported for CL/P, and they represent an unprecedented demonstration of the power of linkage analysis to detect multiple genes simultaneously for a complex disorder.

Animals, Animals, Newborn, Biopsy, Needle, Cell Movement, Disease Models, Animal, Female, Immunohistochemistry, Lung Compliance, Male, Positron-Emission Tomography, Probability, Pulmonary Ventilation, Random Allocation, Respiratory Distress Syndrome diagnostic imaging, Sensitivity and Specificity, Tidal Volume, Neutrophils physiology, Positive-Pressure Respiration methods, Respiratory Distress Syndrome pathology, and Respiratory Distress Syndrome therapy

Objectives: To compare the effects of low vs. high tidal volume (Vt) with three positive end-expiratory pressure (PEEP) strategies on activated neutrophil influx into the lung.
Design: Prospective, randomized controlled animal study.
Setting: Animal laboratory in a university hospital.
Subjects: Newborn piglets.
Interventions: Surfactant-depleted piglets were randomized in littermate pairs; to PEEP of either 0 (zero end-expiratory pressure [ZEEP]; n = 6), 8 cm H2O (PEEP 8; n = 5), or 1 cm H2O above the lower inflection point (LIP) (PEEP>LIP; n = 6). Within each pair piglets were randomized to a low VT (5-7 mL/kg) or high VT strategy (17-19 mL/kg). After 4 hrs of mechanical ventilation, 18-fluorodeoxyglucose (18FDG) was injected and positron emission tomography scanning was performed.
Measurements and Main Results: VT and PEEP changes on influx constants of 18FDG were assessed by analysis of variance. A within-litter comparison of Vt was nonsignificant (p = .50). A between-litter comparison, ordered in linear trend rank, from ZEEP, to PEEP 8, to PEEP>LIP, showed a strong effect of PEEP on influx constant (p = .019).
Conclusions: PEEP set above the LIP on the inspiratory limb of the pressure-volume curve affords a stronger lung protection than VT strategy.

Adult, Comorbidity, Ethnicity, Female, Humans, Interview, Psychological, Male, Obsessive-Compulsive Disorder complications, Prevalence, Schizophrenia epidemiology, Schizophrenia ethnology, Schizophrenic Psychology, South Africa epidemiology, Obsessive-Compulsive Disorder epidemiology, and Schizophrenia complications

Obsessive compulsive disorder (OCD) has been reported in up to 31% of schizophrenia sufferers. This study evaluated the presence of OCD in a Xhosa-speaking schizophrenia group. Xhosa patients (N = 509, including 100 sibships) with schizophrenia were recruited from hospital and community settings. The patients underwent a structured clinical interview for the presence of lifetime co-morbid schizophrenia and OCD. Only 3 patients (0.5%) fulfilled criteria for OCD. No concordance for OCD was noted in the sibship group. Our findings differ from those in other parts of the world, and if replicated, might suggest unique protective environmental or genetic factors for OCD in certain ethnic groups.

Adaptation, Psychological, Adult, Age Distribution, Comorbidity, Female, HIV Infections psychology, Health Care Costs statistics numerical data, Health Care Surveys, Health Expenditures statistics numerical data, Health Services statistics numerical data, Health Status, Health Surveys, Humans, Male, Middle Aged, Ontario epidemiology, Prevalence, Quality of Life, Risk Factors, Sex Distribution, Socioeconomic Factors, Depression economics, Depression epidemiology, HIV Infections economics, and HIV Infections epidemiology

As new technologies extend the lives of people living with HIV/AIDS (PHA), the need increases for services that optimize their quality-of-life cost effectively. This study of PHAs (n = 297) in Ontario, Canada, examined the prevalence of depression, and its association with quality-of-life, coping strategies, social support, and use of health and social services. Results showed that depression was widespread (54.2%) and largely unrelated to demographic characteristics, but associated with diminished health status, health-related quality-of-life, and coping strategies. Depressed PHAs used significantly more crisis health care and related services, and community-based HIV/AIDS service organizations (ASOs). Findings suggest quality-of-life of PHAs may be improved by expanding the capacity of ASO workers to recognize and address depression, including helping depressed PHA access appropriate medication and sustain medication regimes.

Humans, Information Management standards, Library Associations standards, Professional Role, United States, Information Storage and Retrieval standards, Librarians, Libraries, Hospital standards, and Library Services standards

Adolescent, Base Sequence, Child, Child, Preschool, Choristoma genetics, Chromosomes, Human, X, Gene Duplication, Human Growth Hormone deficiency, Humans, Infant, Male, Molecular Sequence Data, Mutation, Pedigree, Phenotype, Pituitary Gland, Anterior, Polymorphism, Genetic, SOXB1 Transcription Factors, DNA-Binding Proteins genetics, High Mobility Group Proteins genetics, Hypopituitarism genetics, Pituitary Gland, Posterior abnormalities, and Transcription Factors genetics

Duplications of Xq26-27 have been implicated in the etiology of X-linked hypopituitarism associated with mental retardation (MR). Additionally, an expansion of a polyalanine tract (by 11 alanines) within the transcription factor SOX3 (Xq27.1) has been reported in patients with growth hormone deficiency and variable learning difficulties. We report a submicroscopic duplication of Xq27.1, the smallest reported to date (685.6 kb), in two siblings with variable hypopituitarism, callosal abnormalities, anterior pituitary hypoplasia (APH), an ectopic posterior pituitary (EPP), and an absent infundibulum. This duplication contains SOX3 and sequences corresponding to two transcripts of unknown function; only Sox3 is expressed in the infundibulum in mice. Next, we identified a novel seven-alanine expansion within a polyalanine tract in SOX3 in a family with panhypopituitarism in three male siblings with an absent infundibulum, severe APH, and EPP. This mutation led to reduced transcriptional activity, with impaired nuclear localization of the mutant protein. We also identified a novel polymorphism (A43T) in SOX3 in another child with hypopituitarism. In contrast to findings in previous studies, there was no evidence of MR or learning difficulties in our patients. We conclude that both over- and underdosage of SOX3 are associated with similar phenotypes, consisting of infundibular hypoplasia and hypopituitarism but not necessarily MR.

Adaptation, Psychological, Chi-Square Distribution, Community Health Services economics, Cross-Sectional Studies, Depression virology, Female, Financing, Personal statistics numerical data, HIV Infections complications, HIV Infections epidemiology, Health Care Surveys, Health Expenditures statistics numerical data, Health Services Needs and Demand, Health Status, Health Surveys, Humans, Karnofsky Performance Status, Male, Ontario epidemiology, Poverty psychology, Poverty statistics numerical data, Quality of Life, Social Work statistics numerical data, Socioeconomic Factors, Surveys and Questionnaires, Community Health Services statistics numerical data, HIV Infections psychology, Patient Acceptance of Health Care psychology, and Patient Acceptance of Health Care statistics numerical data

Community-based AIDS service organizations (CBAOs) direct services to multiple-needs people living with HIV/AIDS who are less likely to use mainstream health promotion services. As people live longer with HIV, the potential to enhance quality of life increases, yet little is known about who uses CBAOs or how this use affects other health and social services. This study of people living with AIDS in Ontario, Canada (n = 297) examined the demographic and health-related characteristics of people with AIDS who do and do not use CBAOs and their patterns of mainstream service utilization. It found that users of CBAOs were significantly less healthy, less able to sustain normal activities, and more often depressed. They reported physical disabilities significantly more often. Their quality of life was also lower along certain dimensions. They were significantly poorer and more reliant on government income supports. They consumed significantly more nonhospital health and social services and had significantly higher out-of-pocket costs. These results suggest CBAOs are being accessed appropriately by those most vulnerable. In an effort to strengthen CBAO capacity to recognize and address depression and physical health problems prevalent among their clients, links to other mainstream health promotion and social services is recommended.

Australia, Chromosome Mapping, Europe, Family, Genetic Markers genetics, Genomics methods, Humans, Middle Aged, United States, Chromosomes, Human genetics, Genetic Linkage, Genetic Predisposition to Disease genetics, Genetic Testing methods, and Multiple Sclerosis genetics

To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis. Multipoint nonparametric linkage analysis revealed highly significant linkage in the major histocompatibility complex (MHC) on chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18). This set of markers achieved a mean information extraction of 79.3% across the genome, with a Mendelian inconsistency rate of only 0.002%. Stratification based on carriage of the multiple sclerosis-associated DRB1*1501 allele failed to identify any other region of linkage with genomewide significance. However, ordered-subset analysis suggested that there may be an additional locus on chromosome 19p13 that acts independent of the main MHC locus. These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for multiple sclerosis will have to involve large sample sizes and an association-based methodology.

Adult, Aged, Cohort Studies, Disability Evaluation, Female, Humans, Inpatients, Longitudinal Studies, Male, Middle Aged, Ontario, Patient Transfer, Predictive Value of Tests, Probability, Prospective Studies, Recovery of Function, Risk Factors, Socioeconomic Factors, Treatment Outcome, Activities of Daily Living, Continuity of Patient Care organization administration, Patient Discharge, Physical Therapy Modalities, and Rehabilitation Centers organization administration

Objective: To determine which sociodemographic and clinical characteristics of patients admitted to a general activation service (GAS) are predictive of discharge to patients' discharge goal locations (DGLs).
Design: Prospective cohort study.
Setting: Rehabilitation and complex continuing care hospital in southern Ontario, Canada.
Participants: Patients admitted from January 2000 to December 2002 (N=154).
Intervention: The GAS.
Main Outcome Measure: Patients indicated on their service applications where they wanted to be discharged. This is termed the DGL.
Results: Fifty-three percent of the sample were discharged to their DGLs. Ninety-eight percent of these patients were discharged by 9 months. Eighty-seven percent who were discharged to their DGLs were discharged to their own home. Predictors of being discharged to the DGL were better activities of daily living scores, good vision, and having sufficient help at home. Expert clinician opinion of the likelihood of each patient being discharged to his/her DGL, based on initial assessment, was also predictive of each patient's eventual discharge to his/her DGL.
Conclusions: The GAS has a 53% success rate in discharging patients to their DGLs. Variables have been identified that should be useful in predicting whether patients will be discharged to their DGLs. Our findings are meaningful and informative in determining future admission criteria for the service.

Adult, Antipsychotic Agents therapeutic use, Humans, Hysteria drug therapy, Male, Religion and Psychology, South Africa, Syndrome, Culture, Hysteria psychology, and Hysteria rehabilitation

Adult, Chi-Square Distribution, Demography, Factor Analysis, Statistical, Family Health, Female, Humans, Male, Middle Aged, Schizophrenia complications, Severity of Illness Index, South Africa epidemiology, Psychiatric Status Rating Scales, Schizophrenia diagnosis, Schizophrenia epidemiology, Schizophrenic Psychology, and Sibling Relations

Careful phenotyping and the identification of subtypes of schizophrenia can contribute significantly to the success of genetic studies in schizophrenia. The phenomenology of schizophrenia in affected sib pairs has been well-described in Caucasian populations, however a paucity of data exists for African populations. This study therefore investigated symptom dimensions in a sizeable group of affected Xhosa sib pairs as a means of evaluating the role of shared familial factors in the psychosis of schizophrenia. Five hundred and thirteen participants were interviewed with the Diagnostic Interview for Genetic Studies (DIGS), which included the Schedules for the Assessment of Negative and Positive symptoms (SANS/SAPS). One hundred and four sib pairs were then extracted (N = 208) for analysis of concordance for lifetime psychotic symptoms and an exploratory factor analysis of the SANS/SAPS. Concordance analysis of life-time symptoms indicated a significant concordance for olfactory hallucinations, persecutory delusions, jealousy, somatic, reference and control delusions as well as thought insertion and withdrawal. The factor analysis of the global scores of the SAPS and SANS revealed a five factor best-fit model and accounted for 92.5% of variance. The factors included a negative symptom factor, a positive symptom factor, a positive thought disorder and a bizarre behaviour component. The core symptomatology of schizophrenia in this sib pair sample was similar to that reported in Caucasian populations with the exception of higher rates of auditory hallucinations and delusions of persecution. In summary therefore; although the factor analysis only supported the concept of the universality of psychotic symptoms in schizophrenia, the concordance analysis of these symptoms did reveal hallucinations as well as delusions of control as possible candidates relevant for future research into genotype-phenotype relationships.

Antineoplastic Agents chemical synthesis, Humans, Microtubules drug effects, Molecular Structure, Structure-Activity Relationship, Triazoles chemical synthesis, Tubulin Modulators chemical synthesis, Tumor Cells, Cultured, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Triazoles chemistry, Triazoles pharmacology, Tubulin Modulators chemistry, and Tubulin Modulators pharmacology

A novel triazole-containing chemical series was shown to inhibit tubulin polymerization and cause cell cycle arrest in A431 cancer cells with EC(50) values in the single digit nanomolar range. Binding experiments demonstrated that representative active compounds of this class compete with colchicine for its binding site on tubulin. The syntheses and structure-activity relationship studies for the triazole derivatives are described herein.

Community-Acquired Infections epidemiology, Drug Resistance, Bacterial, Electrophoresis, Gel, Pulsed-Field, Florida epidemiology, Humans, Staphylococcus aureus isolation purification, Washington epidemiology, Wound Infection epidemiology, Wound Infection microbiology, Community-Acquired Infections microbiology, Methicillin pharmacology, Methicillin Resistance, Staphylococcal Infections epidemiology, and Staphylococcus aureus drug effects

We examined 299 methicillin-resistant, community-associated Staphylococcus aureus isolates from Florida and Washington State for the presence of the USA300 epidemic clone. Pulsed-field gel electrophoresis demonstrated the epidemic clone in 43% of our S. aureus strains and in isolates from both states. The majority of the USA300 isolates (88%) were from wound infections.

Animals, Antimitotic Agents chemistry, Antimitotic Agents classification, Biopolymers chemistry, Biopolymers metabolism, Cell Line, Tumor, Humans, Inhibitory Concentration 50, Mice, Molecular Structure, Oxadiazoles chemical synthesis, Oxadiazoles classification, Protein Conformation drug effects, Structure-Activity Relationship, Antimitotic Agents chemical synthesis, Antimitotic Agents pharmacology, Oxadiazoles chemistry, Oxadiazoles pharmacology, Tubulin chemistry, and Tubulin metabolism

Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 microM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC(50)=7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents.

Administration, Oral, Animals, Antioxidants administration dosage, Ascorbic Acid administration dosage, Dose-Response Relationship, Drug, Female, Fetal Weight drug effects, Gestational Age, Methacholine Chloride pharmacology, Phenylephrine pharmacology, Pregnancy, Rats, Rats, Mutant Strains, Vasoconstrictor Agents pharmacology, Vasodilator Agents pharmacology, Vasomotor System drug effects, Antioxidants pharmacology, Ascorbic Acid pharmacology, Ascorbic Acid Deficiency physiopathology, Mesenteric Arteries physiopathology, Pregnancy Complications physiopathology, and Vasomotor System physiopathology

Plasma ascorbic acid is decreased in women with the pregnancy disorder preeclampsia. We used a mutant strain of rats (Osteogenic Disorder Shionogi), dependent on dietary sources of vitamin C, to investigate whether reduced intake of the vitamin would differentially affect vascular function in late-pregnant (day 19) and age-matched virgin rats. The animals were given either 1 mg/mL of ascorbic acid ad libitum in drinking water [fully supplemented (FS)] or 0.25 mg/mL [marginally supplemented (MS)]. Fetal weights were 21% lower in MS than FS rats, whereas mean maternal weights and pup numbers did not differ. Small mesenteric arteries (diameter, 268+/-7 microm) were mounted in a pressurized arteriograph. Myogenic reactivity (contractile response to step increases in intraluminal pressure) was increased in arteries from MS pregnant compared with FS pregnant rats to levels observed in virgin rats. Ascorbic acid intake did not affect myogenic responses of arteries from virgin rats. Hence, the normal pregnancy-induced reduction in myogenic reactivity was abrogated in MS pregnant animals. Inhibition of nitric oxide synthase had no effect on the myogenicity of arteries from virgin or MS pregnant rats but increased myogenicity of FS pregnant rats to the level of MS pregnant rats. Free radical scavengers reversed the accentuated myogenicity of MS pregnant rats without affecting FS pregnant or virgin rat arteries. These data indicate that moderate ascorbate deprivation increases mesenteric artery myogenic responsiveness during pregnancy. This increase may result from a decrease in nitric oxide-mediated modulation of the myogenic contractile response.

Adenosine Triphosphate metabolism, Azepines chemistry, Binding Sites, Cell Proliferation drug effects, Cells, Cultured, Humans, Molecular Structure, Phosphorylation drug effects, Protein Kinase Inhibitors chemistry, Protein Serine-Threonine Kinases antagonists inhibitors, Protein-Tyrosine Kinases antagonists inhibitors, Receptor, ErbB-2 antagonists inhibitors, Structure-Activity Relationship, Substrate Specificity, Azepines chemical synthesis, Azepines pharmacology, ErbB Receptors antagonists inhibitors, Protein Kinase Inhibitors chemical synthesis, and Protein Kinase Inhibitors pharmacology

A novel class of pyrimido[4,5-b]-1,4-benzoxazepines is described as inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase. Two compounds display potent EGFR inhibitory activity of less than 1 microM in cellular phosphorylation assays (IC(50) 0.47-0.69 microM) and are highly selective against a small kinase panel. Such compounds demonstrate anti-EGFR activity within a class that is different from any known EGFR inhibitor scaffolds. They also provide a basis for the design of kinase inhibitors with the desired selectivity profile.