Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are a number of reports suggesting that neurological disorders may be due to infectious agents, such as viruses. In order to study the role of viruses on cellular plasticity in the central nervous system, we established a model of virus infection in the mouse. Inoculation of mouse with canine distemper virus (CDV) led to an acute encephalitis, late neurological disorders and an obesity syndrome. To analyse the role of viral replication on the development of this syndrome we studied the cerebral distribution of viral products during the course of infection. Viral proteins and RNA accumulated in mouse brain from the 9th day to the 6th week post-inoculation, particularly in hypothalamus, a cerebral structure implicated in obesity. Such selective viral tropism may explain some of the unexpected features of viral-induced disorders.
 ...
PMID:[Demonstration of viral proteins and RNA in hypothalamus of mice infected by canine distemper virus]. 177 59

A case of hypothalamic encephalitis proved by postmortem examination is reported. The patient was a three-year-old Chinese boy who had complained of obesity for one year and fever for half a year. Three days after admission to a hospital, the patient suddenly died of allergic reaction to intramuscular penicillin, without additional complaints. Autopsy revealed severe bilateral outfall of neurons in the ventromedian hypothalamic nuclei with diffuse hyperplasia of astrocytes and some glial nodules consisting chiefly of oligodendroglias and perivascular cuffing. Similar changes were noticed in hypothalamus at the level of optic chiasm, but the posterior hypothalamic nuclei and lateral hypothalamic nuclei were intact. This article provides significant data for the study of hypothalamic function.
 ...
PMID:Hypothalamic encephalitis with oligodendrocytic glial nodules. Case report of a Chinese boy. 187 13

Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of animals from birds to primates. The neuropathology after experimental infection is similar to that in natural disease but the inflammatory changes are more diffuse. In the rat and mouse, a persistent/tolerant infection can also be induced, in which inflammatory changes are conspicuously absent. In the course of persistent infection of the rat, an elective, focal degeneration ensues that involves the dentate gyrus, retina, and, less frequently, the magnocellular part of the hippocampus. The cytopathic destruction of the dentate gyrus is the likely anatomical substrate of learning deficiencies and behavioral changes, prominent features of chronic infection. Later in infection, more diffuse and random degeneration of neurons can be found. In all species infected, viral antigens are produced in excess and fill all neuronal processes. Beside neurons, glial cells are infected as well. The agent spreads in the nervous system axonally and transsynaptically (transneuronally). The type of neurotransmitter receptors in the synapse and their interaction with viral proteins may modulate the spread of infection (Gosztonyi et al. 1994). Virus particles have not been visualized in the brain in any phase of the disease. During persistent infection of the rat, production of viral proteins has a phasic character. Some rats survive acute infection and develop an obesity syndrome. The anatomical basis of this syndrome is not fully clarified; inflammatory destruction of the infundibular region, vacuolar degeneration of the paraventricular nucleus of the hypothalamus and severe, progressive involution of the hippocampal formation most probably play an important role in the production of this neuroendocrine syndrome. In the acute disease, inflammatory reaction can severely aggravate virus-induced cytopathology, but cannot be the sole cause of the neurological disease, since infection with high passage virus can lead to a similarly severe disease in the absence of inflammatory changes.
 ...
PMID:Borna disease--neuropathology and pathogenesis. 778 50

Paramyxoviruses such as measles virus or canine distemper virus are etiological agents for acute and chronic encephalitis (measles inclusion body encephalitis, subacute sclerosing panencephalitis and chronic distemper encephalitis or old dog encephalitis). The mechanisms by which viral injury leads to neurological diseases have not yet been fully elucidated. We have developed an experimental model in mice in order to analyze the spatial and temporal distribution of canine distemper virus in the central nervous system. Cerebral target structures for viral replication were examined for the presence of viral material (proteins and mRNA) during the two stages of the biphasic disease. During the acute stage of infection all target areas could be identified by day 6 with a similar anatomical distribution in all the animals examined, which were either intracranially or intracerebroventricularly infected. Viral mRNA and proteins were selectively localized in certain brain structures such as the thalamus, hypothalamus, substantia nigra (pars compacta), locus ceruleus and raphe nuclei (dorsalis and centralis), and limbic system (hippocampus, septum, entorhinal and cingulate cortex, amygdala). The virus was apparently unable to replicate in cerebellum, striatum, a large part of cortex, or endothelial cells. During the subacute disease, viral material was no longer detectable except in a few structures such as hypothalamus up to 4-6 weeks after inoculation. After this time, all target structures were devoid of any labeling in spite of the occurrence of pathology (obesity, paralysis) during this viral quiescent phase. These results suggest that after the initial viral exposure, expression of viral genes in defined structures might disrupt central homeostasis and finally may lead to neurological or neuroendocrine diseases, even in the absence of the hallmarks of the virus.
 ...
PMID:Brain structures selectively targeted by canine distemper virus in a mouse model infection. 836 Jul

Experimental infection of mouse brain with a neuroadapted strain of canine distemper virus (CDV) leads to early acute encephalitis, followed by late neurological diseases such as motor pathologies (paralysis and turning behavior) or obesity syndrome. We have previously shown that, during the early stage of infection, CDV replicates transiently in selective structures of the brain including the substantia nigra, a structure known to play a critical role in motor control. In this study we demonstrate that CDV replication in the substantia nigra induces an early decrease in transcript level of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. The CDV infection of neuroblastoma cell culture, constitutively expressing TH, results in downregulation of TH transcription in the absence of cell death. In the few surviving mice with motor deficiencies, a pronounced decrease in TH expression is associated with a loss of dopaminergic cell bodies in the absence of any viral transcripts and proteins, suggesting that the initial CDV infection was sufficient to trigger irreversible neurodegenerative processes.
 ...
PMID:Inhibition of tyrosine hydroxylase expression within the substantia nigra of mice infected with canine distemper virus. 918 58

It is currently well established that the nervous, endocrine and immune systems inter-communicate using biologically active soluble factors, synthesised and produced by these three systems themselves (e.g. immunomodulator effect of hormones, effect of substances secreted by immune cells on endocrine function.). In addition, these systems jointly express receptors for hormones, peptides, growth factors and cytokines. Immuno-neuroendocrine interactions therefore underlie physiological processes and their deregulation can result in various pathological states. By entering into complex relationships with the specialized and differentiated cells of these three systems viruses can alter inter-cellular communication and result in the appearance of pathological processes directly linked to these disturbances. In order to understand the role of viruses in the genesis of neuroimmunoendocrine pathologies, we have developed a cerebral infection model using canine distemper virus (CDV). In infected mice, this paramyxovirus, closely related to the human measles virus, induces early neurological pathologies (encephalitis) which are associated with active viral replication. Mice surviving the acute phase of infection exhibit motor deficits (paralysis and turning behaviour) or obesity during the viral persistence phase, despite the fact that the virus is no longer detectable. The obesity is characterised by hyperinsulinaemia, hyperleptinaemia and hyperplasia of the adipocytes, associated with decreased expression of the OB-Rb hypothalamic leptin receptor and modulated expression of hypothalamic monoamines and neuropeptides. These results support the viral "hit and run" theory, since the initial viral impact in the hypothalamus may be the origin of the changes in later immunoneuroendocrine communication. Thus, certain human neurodegenerative or neuroendocrine diseases may have a previous viral infection aetiology without it being possible to clearly identify the agent responsible.
 ...
PMID:[Viruses and the neuroendocrine system: model of murine obesity induced by cerebral infection by canine distemper virus]. 1037 79

Viruses can induce progressive neurologic disorders associated with diverse pathological manifestations, and therefore, viral infection of the brain can impair differentiated neural functions, depending on the initial viral tropism. We have previously reported that canine distemper virus (CDV) targets certain mouse brain structures, including the hypothalamus, early and selectively. Infected mice exhibit acute encephalitis, with late disease, characterized by motor impairment or obesity syndrome, appearing in some of the surviving mice several months after the initial viral replication. In the present study, we show viral persistence in the hypothalami of obese mice, as demonstrated by low, but still significant, levels of CDV nucleoprotein transcripts, associated with a dramatic decrease in F gene mRNAs. Given the pivotal role of the hypothalamus in obesity (eating behavior, energy consumption, and neuroendocrine function) and that of leptin, the adipose tissue-derived satiety factor acting through hypothalamic receptors, we analyzed the leptin networks in both obese and nonobese mice. The discrepancy found between the chronic and dramatic increase in blood leptin levels and the occurrence of obesity may be due to leptin resistance in the brain. In fact, expression of the long leptin receptor isoform, representing the functional leptin receptor, was specifically downregulated in the hypothalami of obese mice, explaining their inability to generate an adequate response to leptin in the brain. Intriguingly, during the acute phase of infection, its expression was increased in CDV-targeted structures in all infected mice and remained high in obese mice in all CDV-targeted structures, except for the hypothalamus. The biphasic change in hypothalamic leptin receptor expression seen during the progression of CDV-induced obesity provides a new paradigm for understanding mechanisms of neuroendocrinological, virus-induced abnormalities.
 ...
PMID:Alteration of the leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus. 1043 20

HIV infection was first reported in 1981 in USA. It has been 20 years since then. Owing to understandings of pathogenesis of this disease and development of new drugs such as the HIV-specific protease inhibitor (PI), prognosis of disease has been tremendously improved. Especially after 1997 in Japan, the strategy of anti-HIV treatment shifted from two drugs combination to three drugs combination, which is called highly active antiretoviral therapy (HAART). HAART was so effective that prevalence of HIV associated opportunistic infections were decreased dramatically. Mortality among hospitalized HIV-infected patients was decreased from 6.7% in 1996 to 2.6% since then in ACC. However, 80% of patients receiving HAART suffered from side effects and 15% of them had to be changed their treatment due to side effects. Furthermore, an unexpected side effect, namely lipodystrophy syndrome (LDS), was emerged among patients who were receiving HAART more than one year. LDS was first reported as re-distribution of lipid such as central obesity with or without lipo-atrophy from extremities and/or face. Now only cosmetic change, but also it is associated with elevation of lipid and glucose level. Therefore, those patients who have LDS are in face of the risk for the ischemic heart diseases. Our survey indicated that the rate of LDS in Japanese patients were almost same as that of Caucasian patients reported elsewhere. Opportunistic infections associated with HIV infection Treatment for HIV infection consists of two major arms; one is use of anti-HIV drugs to prevent development of AIDS described above and the other is diagnosis, treatment, and prophylaxis of opportunistic infections. There are five very important opportunistic infections; Pneumocystis carinii pneumonia (PCP), cryptococcus meningitis, toxoplasma encephalitis, cytomegalovirus (CMV) infection, and Mycobacterium avium complex (MAC) bacteremia. Because if these five were able to diagnose, a patient can survive under appropriate treatment. On the other hand, if these were not diagnosed, patient must be AIDS death. After introducing HAART, number of CMV retinitis, MAC bacteremia, and AIDS dementia complex were decreasing. However, number of PCP sustained high because PCP is the first indicator disease of AIDS if the patient did not know his HIV status. The first choice of drug is sulfamethoxazole/trimethoprim (ST) for PCP treatment. If the patient were in severe respiratory failure, corticosteroid is used concomitantly. Treatment is usually continued for 3 weeks. We have successfully treated 45 out of 47 cases of PCP for 4 years. However, those patients treated with ST for 3 weeks were limited only 35% because of very high rate of side effects of ST. If the patient was intolerant to ST, treatment was switched to pentamidine. After finishing the treatment, the patient is to be treated with a 5-day course of oral desensitization to ST. More than 80% of patients who were previously intolerant to ST became successfully getting tolerance by this method.
 ...
PMID:[Pulmonary complications in patients with AIDS]. 1185 78

We report the case of a 49-year-old man who was admitted for progressive behaviorial disorders with frontal elements. There was no sensorial nor motor deficiency. Clinical examination revealed android obesity, cutaneous and mucous paleness, pubic and axillary depilation and gynecomastia. Encephalic MRI found a lesion of the left amygdalian region with high T2 intensity and low T1 intensity associated with gadolinium-enhancement. Cerebrospinal fluid analysis showed a lymphocytic meningitis. Panhypopituitarism was found on the endocrine investigations. Anti-RI antibodies were positive, leading to the diagnosis of paraneoplastic limbic encephalitis. The CT-scan showed a node of the lower part of the thymic area. Surgical resection revealed an ectopic mediastinal seminoma. The evolution consisted of paraneoplastic fever and crossed-syndrome with right hemiparesia and left common oculomotor nerve paralysis. Treatment was completed by two cycles of carboplatin, corticosteroids and substitutive opotherapy. Paraneoplastic fever disappeared, but behavioral disorders and palsy remain unchanged. The patient died two years later in a bedridden state. This case of paraneoplastic limbic encephalitis associated with positive anti-RI antibodies and mediastinal seminoma is exceptional and has not to our knowledge been described in the literature. Cancers usually associated with anti-RI antibody are breast and lung cancer. Paraneoplastic limbic encephalitis is not the classical clinical presentation, which usually is brainstem encephalitis. Hypothalamic involvement, uncommon in paraneoplastic limbic encephalitis is mainly associated with positive antineuronal anti-Ma2 antibodies. Finally, the gadolinium enhancement on encephalic MRI is unusual in paraneoplastic limbic encephalitis.
 ...
PMID:[Paraneoplastic limbic encephalitis with positive anti-RI antibodies and mediastinal seminoma]. 1856 62

Toll-like receptors (TLRs) form a large family of pattern recognition receptors with at least 11 members in human and 13 in mouse. TLRs recognize a wide variety of microbial components and potential host-derived agonists that have emerged as key mediators of innate immunity. TLR signaling also plays an important role in the activation of the adaptive immune system by inducing proinflammatory cytokines and upregulating costimulatory molecules of antigen presenting cells. The dysregulation of TLR signaling may cause autoimmunity. This review discusses the contribution of TLR signaling to the initiation and progression of autoimmune diseases, such as rheumatoid arthritis, experimental autoimmune encephalitis, myocarditis, hepatitis, kidney disease, systemic lupus erythematosus, diabetes, obesity, and experimental autoimmune uveitis as well as aging. The involvement of TLR signaling in the pathogenesis of autoimmune diseases may provide novel targets for the development of therapeutics.
 ...
PMID:The critical role of Toll-like receptor signaling pathways in the induction and progression of autoimmune diseases. 1935 17


1 2 3 Next >>