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PubMed2004

Diagnostic microarray: an array of possibilities for parasitology.

Parasites affect a majority of the world's population. Despite this fact, dreams of developing vaccines remain far off. Scientists have long studied gene expression as a hallmark of gene activities reflecting current cell conditions. Analyzing differentially expressed genes is a major initiative, and most labs recoil at the amount of time and high costs required obtaining results. By employing microarrays, researchers can decrease their reliance upon time consuming techniques; consequently, microarray is beginning to dominate other molecular diagnostic technologies. Moreover, the ability of microarrays to monitor simultaneous gene expression of thousands of genes and to produce broad arrays of data has the potential to shift the resources of the scientists from data gathering to analyzing data that are already available. As microarray technology improves and its cost decreases, the role of ability to "see" the molecular biology pathways involved in parasite host relationships will place this technology at the forefront of parasite research.

Animals↗
PubMed2004

Ufd2, a novel autoantigen in scleroderma, regulates sister chromatid separation.

The characterization of molecules recognized by patients with autoimmune diseases has provided significant insights into important biological pathways. In these studies, we define Ufd2 (a novel E4 polyubiquitylating enzyme) as a new autoantigen in scleroderma, and show that it regulates chromosome condensation and separation during mitosis in human cells. Ufd2 is regulated by phosphorylation in mitosis. Inhibition of Ufd2 expression results in mitotic arrest at the metaphase-anaphase transition, where cells manifest abnormal chromosome morphology, missegregated chromosomes, irregular spindles, and premature separation of sister chromatids. This is accompanied by premature separase activation, and accumulation of securin in a novel modified form. We further demonstrate that Ufd2 directly and efficiently ubiquitylates securin in vitro and is required for securin polyubiquitylation in vivo. This is the first description of a physiologic substrate for Ufd2, establishing this E4 enzyme as an important regulator of chromosome condensation and separation during mitosis in human cells. Its targeting in scleroderma, together with many other components of the mitotic machinery, reinforces the concept that mitotic cells may be an important focus of the autoimmune response in this disease.

Apoptosis↗
PubMed2005

Period3 structural variation: a circadian biomarker associated with breast cancer in young women.

Circadian disruption has been indicated as a risk factor for breast cancer in recent epidemiologic studies. A novel finding in circadian biology is that genes responsible for circadian rhythm also regulate many other biological pathways, including cell proliferation, cell cycle regulation, and apoptosis. Therefore, mutations in circadian genes could conceivably result in deregulation of these processes and contribute to tumor development, and be markers for susceptibility to human cancer. In this study, we investigated the association between an exonic length variation in a circadian gene, Period3 (Per3), and breast cancer risk using blood samples collected from a recently completed breast cancer case-control study in Connecticut. There were 389 Caucasian cases and 432 Caucasian controls included in our analysis. We found that the variant Per3 genotype (heterozygous + homozygous 5-repeat alleles) was associated with an increased risk of breast cancer among premenopausal women (odds ratio, 1.7; 95% confidence interval, 1.0-3.0). Our finding suggests that the circadian genes might be a novel panel of potential biomarkers for breast cancer and worth further investigation.

Adult↗
PubMed2004

Thioredoxin induction of peripheral blood mononuclear cells in mice in response to a single bout of swimming exercise.

Thioredoxin (TRX) is a stress-inducible protein with diverse intracellular functions, which is expressed under conditions of oxidative stress. Exercise is known to cause oxidative stress by the generation of oxygen radicals from various biological pathways. The purpose of this study was to determine the level of TRX induction of cellular extracts prepared from peripheral blood mononuclear cells after a 30-min swimming exercise in mice. Plasma corticosterone concentration, considered to be a marker for exercise-induced various stress, rose significantly (p < 0.05) 0.5 h after exercise and rapidly dropped down following recovery. The carbonyl proteins as a marker of oxidative stress were significantly (p < 0.05) higher after 6 and 12 h of recovery in cytosolic extracts. The cytoplasm and nucleus TRX expressions were slightly higher to resting values after 12 and 24 h of recovery. The nucleus TRX expression was significantly (p < 0.05) higher after 24 h of recovery. These findings demonstrate that exercise-induced oxidative stress may be associated with increased intracellular TRX expression after 12 and/or 24 h after exercise in peripheral blood mononuclear cells. It is implied that this delayed and prolonged over-expression of TRX may play some roles in response to exercise-induced oxidative stress.

Animals↗
PubMed2004

Emerging role of EGFR-targeted therapies and radiation in head and neck cancer.

The treatment of head and neck cancer has been at the forefront of novel therapeutic paradigms. The introduction of drugs that interact with selective biologic pathways in the cancer cell has generated considerable attention recently. A wide variety of new compounds that attempt to target growth-signaling pathways have been introduced into the clinic. A majority of studies in the clinic have focused on epidermal growth factor receptor (EGFR) antagonists, but future studies will likely build upon or complement this strategy with agents that target angiogenic or cell-cycle pathways. EGFR activation promotes a multitude of important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Since radiation therapy plays an integral role in managing head and neck squamous cell cancer (HNSCC), inhibiting the EGFR pathway might improve our efforts at cancer cure. The challenge now is to understand when the application of these EGFR inhibitors is relevant to an individual patient and how or when these drugs should be combined with radiation or chemotherapy. Are there molecular markers available to determine who will respond to EGFR inhibitors and who should be treated with alternative approaches? What are the mechanisms behind intrinsic or acquired resistance to targeted agents, and how do we prevent this problem? We need to formulate integrated laboratory/clinical research programs that address these important issues.

Antibodies, Monoclonal↗
PubMed2005

Gene expression in kidney cancer is associated with cytogenetic abnormalities, metastasis formation, and patient survival.

Current diagnosis of renal cancer consists of histopathologic examination of tissue sections and classification into tumor stages and grades of malignancy. Until recently, molecular differences between tumor types were largely unknown. To examine such differences, we did gene expression measurements of 112 renal cell carcinoma and normal kidney samples on renal cell carcinoma-specific cDNA microarrays containing 4,207 genes and expressed sequence tags. The gene expression patterns showed deregulation of complete biological pathways in the tumors. Many of the molecular changes corresponded well to the histopathologic tumor types, and a set of 80 genes was sufficient to classify tumors with a very low error rate. Distinct gene expression signatures were associated with chromosomal abnormalities of tumor cells, metastasis formation, and patient survival. The data highlight the benefit of microarrays to detect novel tumor classes and to identify genes that are associated with patient variables and tumor properties.

Adult↗
PubMed2005

[Effects of exogenous nitric oxide on photosynthetic characteristics of poplar leaves under water stress].

Nitric oxide (NO) is an active molecule involved in many biological pathways, but its effects on photosynthesis of tree leaves have not been established yet. This paper studied the effects of exogenous NO, sodium nitroprusside (SNP), on the water status, photosynthesis and scavenging enzyme activities in poplar leaves. Different levels of SNP treatments had remarkable effects on the water content of leaves, which increased with increasing SNP levels. When the SNP level exceeded 500 micromol x L(-1), differences in leaf water content were no longer significant between different SNP treatments. Exogenous NO increased the photosynthesis rate, photochemical efficiency of PSII Fv/Fm, and Fm/Fo and Fv/Fo ratios, and the effects decreased with increasing duration of water stress. The SOD and POD activities in poplar leaves were higher in 1 hour water stress treatment than in 3 h treatment. Treating with SNP could markedly increase POD activity, but SOD activity did not change much. POD and SOD activities increased initially, and then decreased with increasing SNP levels. The results indicated that exogenous NO delayed the accumulation of active oxygen by increasing POD and SOD activities, and thereby, alleviated the effects of water stress on photosynthetic organization of poplar leaves.

Nitric Oxide↗
PubMed1968

Environmental factors in the physiology of abscission.

This paper reviews the physiological effects of the principal environmental factors which can influence the process of leaf abscission. The factors include temperature, light, water, gases, mineral elements, soil conditions, and parasitic organisms. These factors influence a variety of internal physiological conditions and processes which in turn may either accelerate or retard the process of abscission. The most important internal factors include A) sugar, pectin, cellulose, and other carbohydrates; B) energy-yielding respiration; C) enzymic reactions; D) amino acids, purines, and other nitrogenous substances; E) levels of plant hormones; and F) the molecular biological pathway. The current information is consistent with the hypothesis that the environmental factors act in leaf abscission via direct or indirect influences on the synthesis or reaction rate of enzymes.

Journal Article↗
PubMed1991

Modulation of cardiac genes by mechanical stress. The oncogene signalling hypothesis.

In cardiac muscle, the selectivity and specificity of gene regulation by heparin-binding and transforming growth factors resembles the characteristic program of fetal gene induction during myocardial hypertrophy produced by load. Shared by isolated cardiac myocytes and intact hearts, these complex and heterogeneous responses provide intriguing systems, which are distinct from other lineages and models of cell growth, for the study of trophic signal transduction by cellular oncogenes. A functional role for peptide growth factors and other oncogene-encoded proteins in myocardial hypertrophy suggests biological pathways which might usefully be exploited to promote compensatory growth following infarction or to interfere with maladaptive changes during a hemodynamic load.

Actins↗
PubMed1991

[Nitrate derivatives and anesthesia-resuscitation: physiopathologic bases and therapeutic indications].

This review briefly describes the cellular mechanisms of nitrates and the tolerance. Nitrates activate NO production thus GMPc in the smooth muscle cell explaining their vasodilating properties even in absence of an intact endothelium. The biologic pathway of AMPc is stimulated by prostaglandin activated by nitrates. Tolerance to these agents could result from depletion of sulfhydryl radical but also from reflex cardiovascular adaptation. After a brief recall of pharmacokinetic, pharmacodynamic properties are detailed. Therapeutic use in cardiac surgery, non-cardiac surgery, controlled hypotension, aortic surgery, heart failure, unstable angina, myocardial infarction and systolic hypertension in the elderly are discussed.

Anesthesia↗
PubMed1991

Periodicity in metastatic tumour growth demonstrated in the human liver at autopsy. Preliminary report.

The present study is based on 1,069 autopsies made up of stomach, breast, renal and colonic cancer. Periodicity is described in the liver weight index (liver weight/body height) at death in patients with liver metastases. The seasonal variation tended to be more marked in females and among older patients, and it differed with tumour type. A period with maximum deaths tended to follow that of maximum liver weight index. A periodic difference previously reported in a small series of malignant melanomas is thus not an isolated phenomenon. This indicates that basic biological pathways concerned with the control of tumour growth may be involved. How the system works remains an open question.

Age Factors↗
PubMedDate not supplied

[Relationship between reproductive patterns and infant mortality: alternative interpretations].

A secondary analysis of the data of the Mexican National Fertility and Health Survey of 1987 (ENFES for its spanish acronym) was undertaken in order to study the relationship between reproductive patterns and child mortality. A total of 13,216 births and 711 infant deaths occurred 1 to 15 years previous to the survey were studied. The main conclusions are: 1) it is the adverse social, economic and environmental conditions surrounding young mothers (15 to 19 years) which are responsible for the excess mortality found in their children; 2) children of older women (35 and more years) experience increased mortality only in the late fetal period, this suggesting that a biological mechanism is mainly at stake; 3) the relative risks of death of first births, as compared to subsequent ones are generally smaller than one, indicating that first births have a lower probability of dying. The relative risk of death of first born relative to subsequent births, on the other hand, decreases with increasing age at death, suggesting that biological factors such as low birthweight and intrapartum complications are possibly important as well; 4) relative risks of death for short-spaced as compared to well spaced births were found, in general, to decrease from the late fetal to the neonatal and to the postneonatal periods. This points to a biological pathway, possibly via maternal nutrition, for the effect of spacing on child mortality.

Adolescent↗
PubMed1989

Plasma concentrations of adrenocorticotropin-related peptides in lambs injected with ovine corticotropin releasing factor or vasopressin.

Synthetic ovine corticotropin-releasing factor (oCRF) and arginine vasopressin (AVP) were intravenously injected each alone or in combination (each peptide: 1 microgram/kg body weight) in lambs on days 1, 3, 7 and 20 after birth. Plasma samples were collected just before and 10 and 30 min after injection. Plasma concentrations of cortisol and aldosterone were measured. Adrenocorticotropin (ACTH)-related peptides were isolated by Sephadex G50 column chromatography and measured by radioimmunoassay. Three different peaks with an ACTH immunoreactivity were found in lamb plasma: a "big" ACTH molecular form (Mr = 30,000), an "intermediate" (Mr = 8000) and a "little" (Mr = 4500). In 1 and 3 days-old lambs, both CRF and AVP increased preferentially "intermediate" ACTH. In 7 and 20 days-old lambs, an increase in "little" ACTH occurred after CRF whereas "intermediate" ACTH rose after AVP. The rise in plasma levels of different molecular forms of ACTH after stimulation by CRF or AVP could suggest that the biological pathway of ACTH synthesis, storage and release may occur in different intracellular pools or rather in different pituitary cells. Intermediate ACTH stimulated adrenal secretion of cortisol as soon as the first day of postnatal life and increased plasma aldosterone concentration in 7 and 20 day-old lambs. At these stages aldosterone level did not change after a rise in "little" ACTH.

Adrenocorticotropic Hormone↗
PubMed1987

Assessing social networks and social support in epidemiologic studies.

Epidemiologists and other researchers in the biomedical field have recently recognized the potential importance of social networks and the support they provide in maintaining health and well being. However, measuring social networks and social support has not proven to be easy, measures are generally not well validated and critical dimensions or characteristics of networks have yet to be identified. The aim of this paper is to provide the reader with some background on the work being done in this area. In particular, attention is devoted to why, historically, social networks have been suspected of playing a role in disease causation, what some important characteristics of networks are likely to be, examples of measures currently in use, and what the biological pathways are that may link networks to morbidity and mortality. A description of the Alameda County Study in California is given. In this study, people who were socially isolated were found to be over twice as likely to die in a nine-year follow-up period as those with many contacts. This increased risk was found to be independent of alcohol and cigarette consumption, obesity and other health practices.

Adult↗
PubMed1986

[Degradation of the insecticide parathion in soil].

Degradation of the insecticide Parathion in four types of soil from the Northeast of Brazil has been studied using radiometric techniques. In all the soil samples, sterilized or not, metabolites were detected with Rf values of 0.00 and 0.17 respectively--Silica Gel 60 F254 tlc plates (Merck); solvent system: hexane-acetone (4:1, v/v)--. However, 14CO2 was formed only with the non-sterilized soils and this was independent of the use or not of organic fertilizer. These results suggest that the two metabolites, mentioned above, are formed by a predominantly non-biological pathway, where as the formation of carbon dioxide requires the participation of the microbial flora of the soil. Analysis of the interaction of 14C-Parathion with soils shows that the extent of degradation of this insecticide is modified by adsorption on the soil particles.

Adsorption↗
PubMed1979

Thrombosis: a study of coagulation parameters and mechanisms during allograft rejection.

Thrombosis of the microvasculature has been recognized at the end product of organ rejection, but the exact biological pathway through which this occurs has not been clarified. Normal, factor VII deficient and heterozygous hemophilic (factor VIII) dogs were grouped to study the intrinsic and extrinsic clotting and platelet mechanisms during unmodified renal allograft rejection. The observed alterations of the hemostatic mechanisms are related to the changes observed in the microvasculature. Six groups of donor-recipient animals were studied: Group I -autografts (control); Group II - normal to normal allografts with bilateral nephrectomy; Group III - heterozygotes for factor VIII deficiency; Group IV - normal to normal allografts with unilateral nephrectomy; Group V - normal to factor VII deficiency without nephrectomy; and Group VI - normal to normal allografts with unilateral nephrectomy and dipyridamole. Each engrafted animal was followed pre- and posttransplantation for change in the blood clotting factors, fibrin split products, platelets, white blood cells, renal function and microvasculature. The animals with factor VII deficiency rejected in a similar fashion as the control animals. The group with impaired factor VIII synthesis and platelet function had longer survival times. These data suggest that the intrinsic clotting pathway and platelets are the primary mechanism through which thrombosis occurs secondary to immune injury.

Animals↗
PubMed1982

Ketotifen in the prophylaxis of bronchial asthma.

The pharmacodynamic effects of ketotifen, a benzocycloheptathiophene derivative, on several partly interdependent biological pathways (calcium fluxes in excitable cells, production and release of mediators, mainly SRS-A, smooth-muscle contractility, density and sensitivity of adrenergic receptors) may be relevant to its antianaphylactic and asthma-prophylactic properties. Pharmacological investigations in humans of various target organs (skin, nasal mucosa, bronchi) have shown that ketotifen has strong antihistaminic and antianaphylactic effects. Its inhibiting action on bronchial responsiveness is not limited to bronchospasm induced by allergens but includes certain types of bronchial hyper-reactivity in which known mediators of allergy do not seem to be involved. Some important features of oral asthma prophylaxis with ketotifen are underlined. These include responder rate in both extrinsic and intrinsic asthma, pharmacokinetics and dosage in children, reduction in the consumption of corticosteroids and bronchodilators, and avoidance of side effects.

Asthma↗
PubMed1996

Depression in the patient with chronic pain.

The management of patients with chronic pain is a challenging clinical problem that frequently requires a multi-disciplinary approach. Depression is a common comorbidity associated with chronic pain, occurring in as many as 50% of chronic pain patients. Depression may develop secondarily or independently of the chronic pain syndrome, or it may occur as the primary cause of chronic pain. Regardless of their etiology, evidence exists to suggest that depression and chronic pain share common biologic pathways, namely, the serotonergic (5-HT) and noradrenergic systems. Chronic pain patients who are depressed require aggressive, full-dose treatment with antidepressants. Treatment should be selected based on a prior clinical response, the side-effect profile, the dosing schedule, and the potential for drug interactions. The newer antidepressants, including the selective serotonin reuptake inhibitors venlafaxine and nefazodone, are therapeutic options for the treatment of depression in the patient with chronic pain.

Acute Disease↗