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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inflammatory cytokines tumour necrosis factor-alpha (TNF alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been demonstrated to influence pituitary hormone synthesis directly and via the hypothalamus. Furthermore, IL-6 is produced by some anterior pituitary cells suggesting a paracrine/autocrine role for this cytokine. We show that TNF alpha induces dispersed ovine pituitary cells to produce increased levels of growth hormone (GH) and IL-6 mRNA and secreted IL-6 in a dose and time dependent manner. TNF alpha at concentrations between 1-1000 U/ml increased GH and IL-6 mRNA, relative to control levels, by 5 h post-stimulation. For IL-6, TNF alpha increased specific mRNA at 5 h and 12 h but not 24 h post-stimulation. TNF alpha also induced secreted IL-6 to levels above that spontaneously secreted at all time points from 5 h to 48 h. Levels of common glycoprotein alpha-subunit and follicle stimulating hormone-beta (FSH beta) subunit mRNA were unaffected by TNF alpha. We conclude that TNF alpha can regulate both GH and IL-6 synthesis in dispersed ovine pituitary cells. The implications for paracrine/autocrine control of pituitary hormone synthesis in acute and chronic disease are discussed.
Mol Cell Endocrinol 1992 Mar
PMID:Effects of tumour necrosis factor-alpha on growth hormone and interleukin 6 mRNA in ovine pituitary cells. 163 12

Chronic urticaria is a changeable disorder with an unknown length of duration. Thus, an objective method which could differentiate affected individuals from healthy individuals and with predictive information about when treatment might be diminished or stopped would be desirable. Therefore, we have tried to achieve this by means of Multitest, a device rendering good skin reaction reproduction and reagents such as 48/80 Compound (a nonspecific mast cell degranulator) and histamine. These substances were applied on 1 to 10(3) Mol concentrations for histamine and 10 to 10(3) mg/ml as the degranulating agent. Sixteen patients and 10 controls were submitted to this test, variables such as drugs modifying wheals, time of the day, age range and skin area were controlled. In both groups a clear dose-response relationship was demonstrated by either reagent. However, an excessive individual variability appeared in each sample and significant differences could not be shown so much for sensitivity or for reactivity (responses by the lowest and the highest concentrations, respectively). We conclude that the lack of differences observed on cutaneous mast cell "releasability" and skin vessels response to histamine in chronic urticaria patients could be due to a rather outstanding role of other cells and its mediators, in mechanisms of that chronic disease.
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PMID:Skin reactions to histamine and compound 48/80 in chronic urticaria: a diagnostic tool? 338 11

Asthma is recognized as the most common treatable chronic disease of the lung, afflicting over 100 million people of all age groups yet, despite therapeutic advances, there has been little impact on the rising morbidity and mortality from the disease. This article discusses ways in which molecular medicine can inform public health policy and clinical practice in the management of asthma. It focuses on the recognition that asthma is an inflammatory disorder, and that the public health burden of the disease can be reduced by identifying environmental factors that may trigger asthma in genetically susceptible individuals.
Mol Med Today 1996 May
PMID:Aetiology of asthma: how public health and molecular medicine work together. 879 87

Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, is implicated in the etiology of Balkan endemic nephropathy (BEN), a chronic disease affecting populations in the Balkans. Patients suffering from Balkan endemic nephropathy, urinary-tract tumors, or both are more frequently extensive metabolizers of debrisoquine than persons unaffected by these conditions. As shown previously (Castegnaro et al., Int J Cancer, 77:70-75, 1998), OTA induction of renal tumors is markedly sex- and strain-specific in Dark Agouti (DA) and Lewis rats, with DA males being most responsive and DA females being resistant; only DA females were phenotyped as slow debrisoquine metabolizers. Formation of OTA-related DNA adducts in the kidney was closely correlated with renal carcinogenicity. To elucidate the critical biotransformation enzymes involved in OTA genotoxicity and carcinogenicity, the expression of cytochrome P450s (CYPs) 1A, 2A, 2B, 2C, 2D, and 3A in the kidney and liver microsomes of untreated and OTA-treated DA and Lewis rats (both sexes) was determined by western blot analysis. Chronic OTA treatment was found to modify CYP expression in kidney and liver. In the animals most susceptible to renal OTA carcinogenicity and DNA adduct formation, the OTA-toxifying isoforms (CYPs 2C11, 1A2, and 3A) were highly expressed in the liver, and little of the OTA-detoxifying isoforms (CYPs 1A1 and 2A) was detected. CYP2D was not expressed in DA rats and therefore is not involved in these phenomena. Our results confirm that the strain- and sex-specific genotoxic response of OTA is controlled, in part, by CYP-mediated metabolic reactions that convert OTA into DNA-reactive intermediates.
Mol Carcinog 1998 Oct
PMID:Sex- and strain-specific expression of cytochrome P450s in ochratoxin A-induced genotoxicity and carcinogenicity in rats. 980 61

Current developments in experimental chemotherapy of Chagas' disease are reviewed, in particular the demonstration that fourth-generation azole derivatives (inhibitors of sterol C14alpha demethylase), with particular selectivity against Trypanosoma cruzi and special pharmacokinetic properties, are capable of inducing radical parasitological cures in murine models of both acute and chronic disease. These are the first reports of parasitological cure of this disease in its chronic phase. We also discuss the relevance of etiological treatment in the clinical outcome of patients with chronic Chagas' disease. Although previous studies have suggested an important autoimmune component in the pathogenesis of this disease, recent results obtained using highly sensitive polymerase chain reaction based detection methods and detailed immunological characterization of the inflammatory process associated with chagasic cardiomyopathy indicate a positive correlation between tissue parasitism and the severity of cardiac pathological findings. Effective antiparasitic treatment can lead to regression of the inflammatory heart lesions and fibrosis in experimental animals and to stop the progression of the disease in humans. Taken together, these findings support the notion that the presence of the parasite is a necessary and sufficient condition for chagasic cardiomyopathy and confirm the importance of specific etiological treatment in the management of chronic chagasic patients.
J Mol Med (Berl) 1999 Mar
PMID:Chemotherapy of Chagas' disease: the how and the why. 1009 May 96

Hepadnaviruses (hepatitis B viruses) cause transient and chronic infections of the liver. Transient infections run a course of several months, and chronic infections are often lifelong. Chronic infections can lead to liver failure with cirrhosis and hepatocellular carcinoma. The replication strategy of these viruses has been described in great detail, but virus-host interactions leading to acute and chronic disease are still poorly understood. Studies on how the virus evades the immune response to cause prolonged transient infections with high-titer viremia and lifelong infections with an ongoing inflammation of the liver are still at an early stage, and the role of the virus in liver cancer is still elusive. The state of knowledge in this very active field is therefore reviewed with an emphasis on past accomplishments as well as goals for the future.
Microbiol Mol Biol Rev 2000 Mar
PMID:Hepatitis B virus biology. 1070 74

In the liver, the progressive accumulation of connective tissue, a complex and dynamic process termed fibrosis, represents a very frequent event following a repeated or chronic insult of sufficient intensity to trigger a "wound healing"-like reaction. The fibrotic process recognises the involvement of various cells and different factors in bringing about an excessive fibrogenesis with disruption of intercellular contacts and interactions and of extracellular matrix composition. However, Kupffer cells, together with recruited mononuclear cells, and hepatic stellate cells are by far the key-players in liver fibrosis. Their cross-talk is triggered and favoured by a series of chemical mediators, with a prominent role played by the transforming growth factor beta. Both expression and synthesis of this inflammatory and pro-fibrogenic cytokine are mainly modulated through redox-sensitive reactions. Further, involvement of reactive oxygen species and lipid peroxidation products can be clearly demonstrated in other fundamental events of hepatic fibrogenesis, like activation and effects of stellate cells, expression of metalloproteinases and of their specific inhibitors. The important outcome of such findings as regards the pathogenesis of liver fibrosis derives from the observation of a consistent and marked oxidative stress condition in many if not all chronic disease processes affecting hepatic tissue. Hence, reactive oxidant species likely contribute to both onset and progression of fibrosis as induced by alcohol, viruses, iron or copper overload, cholestasis, hepatic blood congestion.
Mol Aspects Med 2000 Jun
PMID:Pathogenesis of liver fibrosis: role of oxidative stress. 1097 99

Recent attention is focused on understanding the genetic basis for individual susceptibility to the development of chronic disease. An emphasis is concentrated on establishing an association between inheritance of polymorphic chemical metabolizing genes and development of environmental cancer (e.g., lung cancer among cigarette smokers). The early reports of such associations have been very encouraging. However, some reported positive associations were not substantiated in subsequent studies using larger sample sizes and different ethnic populations. In this review, some confounding factors that contribute to the discrepancies are presented (e.g., ethnic-dependent distribution of variant gene alleles, differential expression of metabolizing genes, and inadequate study design). It is possible that the precision of the association can be improved if the mentioned investigations are complemented with concurrent studies of biological activities/effects. The usefulness of integrating metabolic susceptibility with biomarker measurement for understanding the development of lung cancers is presented. The importance of using adequate sample size and experimental design is emphasized. Development of a reliable approach for prediction of environmental disease not only will provide fundamental information regarding the genetic basis of human disease but will be useful for reducing disease burden in the population and for advancing patient care. Environ. Mol. Mutagen. 37:215-225, 2001. &copy 2001 Wiley-Liss, Inc.
Environ Mol Mutagen 2001
PMID:Usefulness of genetic susceptibility and biomarkers for evaluation of environmental health risk. 1131 39

Chronic diseases are the main public health problem in Western countries. There are indications that these diseases originate in the womb. It is thought that undernutrition of the fetus during critical periods of development would lead to adaptations in the structure and physiology of the fetal body, and thereby increase the risk of diseases in later life. The Dutch famine--though a historical disaster--provides a unique opportunity to study effects of undernutrition during gestation in humans. This thesis describes the effects of prenatal exposure to the Dutch famine on health in later life. We found indications that undernutrition during gestation affects health in later life. The effects on undernutrition, however, depend upon its timing during gestation and the organs and systems developing during that critical time window. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. Little is known about what an adequate diet for pregnant women might be. In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations.
Mol Cell Endocrinol 2001 Dec 20
PMID:Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. 1173 98

Osteoarthritis has developed into the most common chronic disease in the highly industrialized nations. Moreover, because of the prevalence of the disease in the elderly, this trend occurs worldwide as a consequence of increasing longevity due to the overall improvement in living conditions and health status. In contrast, research on osteoarthritis is still financially marginalized within biomedical research, so that the molecular and biophysical bases for disease initiation and progression are largely unmapped. The following sequence of five reviews highlights a remarkable change in that body of knowledge taking place at the beginning of the World Health Organization (WHO) 'Bone and Joint Decade 2001-2010'. The data and ideas presented in these articles reflect to some extent the guidelines set up by the WHO and by the National Institutes of Health of the USA and therefore allow a glimpse into the directions that research in osteoarthritis will take in the future.
Cell Mol Life Sci 2002 Jan
PMID:Introduction: molecular and biomechanical basis of osteoarthritis. 1184 30


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