Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood monocytes (PBM) do not possess angiotensin converting enzyme (ACE) activity in the inactive state. However, measurable PBM ACE activity is found in patients with certain inflammatory diseases. We have examined the effect of cytokines likely to be present during granulomatous inflammation on the regulation of ACE mRNA in PBM. The presence of ACE mRNA in human PBM cultured in vitro with various cytokines for up to 6 days was analyzed using polymerase chain reaction. PBM not exposed to cytokines did not express ACE mRNA, while incubation of PBM with recombinant human GM-CSF resulted in high levels of ACE mRNA expression after 72 h of cell culture, which persisted through day six. Increased ACE mRNA expression occurred concomitantly with phenotypic changes in cell size and shape consistent with cell activation. A 5-fold increase in ACE enzymatic activity also occurred. Incubation of PBM with all other cytokines tested failed to induce ACE mRNA expression. Alveolar macrophages expressed ACE mRNA immediately following their isolation, but mRNA expression decreased markedly during a 24-h period of incubation and was only partially reversed with exogenous GM-CSF. We conclude that GM-CSF enhances ACE mRNA levels in human PBM, but not in alveolar macrophages.
 ...
PMID:Angiotensin converting enzyme (kininase II) mRNA production and enzymatic activity in human peripheral blood monocytes are induced by GM-CSF but not by other cytokines. 815 33

We report two siblings with sarcoidosis; the younger sister had symptoms of central nervous system, and both sisters had subcutaneous mass lesions in the gluteal region. Case 1. A 30-year-old woman presented with two episodes of right leg paresis. On admission, neurological examination revealed right leg weakness, spasticity of both legs, increased deep tendon reflexes in all extremities, urinary disturbance and hearing loss of the right ear, but she had no meningeal signs. Serological studies were normal including angiotensin converting enzyme. Cerebrospinal fluid revealed elevated protein to 340 mg/dl, mild pleocytosis, decreased glucose. CSF culture was negative, and cytology showed no malignant cells. Enhanced MR imaging showed diffuse leptomeningeal enhancement in both the brain around basal meninges and the whole spinal cord. Case 2. A 34-year-old woman (the elder sister of Case 1) presented with visual disturbance. She had been diagnosed to have bilateral iritis at Hiroshima Red Cross Hospital before visiting our hospital. Neurological examination and serological studies were normal. In both cases, left gluteal subcutaneous mass was detected and its biopsy revealed characteristic sarcoid nodules and confirmed the diagnosis of sarcoidosis. A tendency of familial occurrence and positive associations of the specific HLA antigens in sarcoidosis have been reported. Though the diagnosis of neurosarcoidosis has been difficult without extraneurological signs, sarcoidosis should be considered as a differential diagnosis in all the patients with myelopathy, and enhanced MRI and measure of CSF angiotensin converting enzyme seem to be useful for diagnosis and evaluation of drug effect during the course of steroid therapy.
 ...
PMID:[Two siblings with sarcoidosis diagnosed by younger sister's central nervous symptoms]. 904 58

The hemorphins are a family of recently identified opioid receptor binding peptides derived from the proteolytic processing of the beta, gamma, delta, and epsilon chains of hemoglobin. They have previously been identified at high concentration in human pituitary glands and in the CSF of patients with cerebral bleeding. Hemorphins are potent inhibitors of angiotensin converting enzyme and therefore possibly have a role to play in blood pressure regulation. We report the presence of four hemorphin peptides in extracts of normal adrenal tissue and in pheochromocytoma tumors. The hemorphins were quantified and structurally characterized using mass spectrometry. High concentrations of hemorphins were found in all samples, comparable with the levels reported in the literature for pituitary and brain tissue.
 ...
PMID:Mass spectrometric identification and quantification of hemorphins extracted from human adrenal and pheochromocytoma tissue. 908 45

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The frequency of neurologic manifestations varies from 5 to 15% of cases. Systemic manifestations of sarcoidosis are often present and the diagnosis is still based on histopathological studies. In nearly half of the patients no systemic manifestations are found and the diagnosis of sarcoidosis may be difficult. Main neurologic involvements are cranial and peripheral nerve lesions. Other manifestations include aseptic meningitis, hydrocephalus, parenchymatous granulomata of the central nervous system, hypothalamic dysfunction and myopathies. There is more than one manifestation of neurosarcoidosis in 30% of the patients. Lumbar puncture is useful to rule out other diseases but CSF changes are not specific, neither elevated serum angiotensin converting enzyme levels. Computed tomography is helpful, but magnetic resonance imaging is the best diagnostic tool. The granulomatous nature of the disease can only be confirmed by tissue sampling and brain biopsies are sometimes required. There have been no controlled trials of treatment for neurosarcoidosis but corticosteroids are the main stay of therapy. The prognosis is often good and 55% of patients reported have had a complete recovery. In case of failure, immunosuppressive and radiation therapy can be used. Surgery is indicated to establish tissue diagnosis, in the presence of increased intracranial pressure, or to remove brain tumor.
 ...
PMID:[Neurosarcoidosis. Review of the literature]. 1056 61

The randomized clinical trial, LU19, conducted by the Medical Research Council Lung Cancer Working Party, was designed to compare ACE (doxorubicin, cyclophosphamide and etoposide) chemotherapy plus G-CSF (granulocyte colony-stimulating factor) at 2-week intervals versus ACE chemotherapy alone at standard 3-week intervals in patients with small-cell lung cancer. This trial investigated whether more intensive administration of ACE would improve overall survival and affect the quality of life of patients. The report on overall survival and other outcome measures will be published in the Journal of Clinical Oncology. In this paper we focus on methods of analysing aspects of data reflecting quality of life. Twelve symptoms of lung cancer and its treatment - cough, haemoptysis, pain, nausea, vomiting, hoarse voice, sore mouth, rash, lethargy, lack of appetite, alopecia, and dysphagia - were scheduled to be assessed on seven occasions for the ACE arm and on eight occasions for the ACE+G-CSF arm by clinicians during the first 18 weeks of the treatment period. However, in practice the number of assessment forms completed per patient ranged from 1 to 9, and assessment time-points were very different from those planned. These 'messy' longitudinal data are explored by both a summary measure approach, in which experience of a symptom is summarized by a single value, and an extensive model-based statistical approach, which explicitly takes into account correlation within repeated measures. These analyses provide a clear picture of symptom comparisons between the two treatments. The application of various methods offers not only an approach to assessing the robustness of the results but also a basis for investigating reasons for inconsistency of results across methods. We conclude that except lethargy, which is worse in the ACE+G-CSF arm, all symptoms are similar across the two arms during the treatment period.
 ...
PMID:Analysis of messy longitudinal data from a randomized clinical trial. MRC Lung Cancer Working Party. 1098 40

Sarcoidosis is a chronic systemic disease of unknown causes characterized by noncauseating granuloma in various organs. Neurological involvement occurs in 5-6% of patients with sarcoidosis. Most patients with neurosarcoidosis have extraneurologic abnormalities and extraneurologic biopsies usually support the diagnosis, however, nearly half of the patients with neurosarcoidosis present with neurological manifestations without systemic symptoms. Several cases of isolated neurosarcoidosis have been reported, making the diagnosis difficult. Although several diagnostic criteria have been proposed, neuropathological examination is required for the definite diagnosis. Brain biopsy may still be required in selected patients. Since it is often difficult to perform, clinical assessment with various combinations of modern neuroimaging techniques is important. Lumbar puncture is useful to rule out other diseases but CSF changes are not specific. Elevated serum ACE level is also not a specific diagnosis test. Any part of the CNS can be involved, but there is predilection for hypothalamus, pituitary gland, leptomeninges, and cranial nerves particularly facial nerve. Although corticosteroids are the main stay of therapy, refractory cases can be treated by immunosuppressive and radiation therapy.
 ...
PMID:[Neurosarcoidosis]. 1223 76

Pulmonary fibrosis can be observed as an end state in a number of chronic inflammatory pulmonary diseases. Although the mechanisms by which lung fibrosis develops are not fully ascertained, recent findings suggest that oxidative stress may play an important role in the pathogenesis of tissue fibrosis affecting apoptosis of both structural and inflammatory cells and altering the cytokine microenvironment balance. Damage and alteration of alveolar epithelial cells is one of the hallmarks of interstitial lung fibrosis. Recently, it has been demonstrated that the presence of oxidative stress may lead to the damage, activation and/or apoptosis of alveolar epithelial cells either directly, through an imbalanced intracellular redox equilibrium, or indirectly, by activating redox-sensitive effector pathways, such as transcription factors and angiotensin converting enzyme, increasing the conversion of angiotensinogen into angiotensin II that can be considered a mediator of oxidative stress, capable of inducing apoptosis. Furthermore, it has been demonstrated that angiotensin II acts as a proinflammatory cytokine and is effective in activating fibroblasts through the release of transforming growth factor (TGF-beta). As well as activation, differentiation, proliferation and apoptosis of fibroblasts seem related to the oxidant/antioxidant balance, and the maintenance of a high intracellular level of reduced glutathione (GSH) is considered crucial in providing a reducing environment within the cell, able to protect against oxidative stress. In those conditions where oxidants, either inhaled or produced by inflammatory cell, increase, the ratio between GSH and oxidized glutathione (GSSH) may lower, influencing a variety of cellular redox-sensitive signaling processes such as the activation of nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) that lead to a transcriptional up-regulation of a number of genes involved in inflammation and/or fibrogenesis, including cytokines [interleukin (IL)-1,, tumor necrosis factor (TNF-alpha), IL-6] chemokines (IL-8), adhesion molecules (VCAM-1, ICAM-1) and growth factors (GM-CSF). In addition, several studies have shown that oxidative stress may also affect the immune response by inducing an up-regulation of HLA-DR as well as the expression of two costimulatory molecules such as CD40 and CD86, determining a persistent state of immune activation, and affecting the Th1/Th2 balance, modulating the T-cell effector response towards the Th2 phenotype. It is clear that a better understanding of the precise sequence of events that make the difference between normal tissue repair and fibrosis, including the role played by oxidative stress, will certainly improve our therapeutic approach to pulmonary fibrosis.
 ...
PMID:Role of oxidative stress in pulmonary fibrosis. 1261 77

Mobilization of bone marrow stem cells by granulocyte-colony-stimulating factor (G-CSF) is considered to be an alternative to invasive transplantation of autologous myoblasts or stem cells directly into injured cardiac tissue. We have started a 24 week randomized open study in order to elucidate effects of G-CSF (filgrastim) on clinical, hemodynamic and neurohumoral status of patients with NYHA class II-IV chronic heart failure due to ischemic heart disease with zones of nonviable myocardium and left ventricular ejection fraction <40% as well as to assess safety of addition of G-CSF to standard therapy with ACE inhibitors and beta-blockers. It is planned to include 20 patients into each filgrastim (5 mg/kg/day) and control (0.9% NaCl) groups. Methods to be used: dobutamine stress echocardiography for detection of myocardial viability, magnetic resonance tomography, 6-minute walk test, quality of life questionnaire. By the present time 5 patients were included (4 in filgrastim and 1 in control group) and passed 3-6 months points. A control patient died suddenly on 11th week. All patients in filgrastim group are alive (1 experienced obvious improvement, 2 remained stable, and 1 deteriorated and required urgent hospitalization). None of the patients had signs of appearance of 'regenerated' myocardial zones. The patient with positive clinical dynamics was characterized by young age (48 years), moderately severe heart failure (NYHA class II) and pronounced leukocyte reaction to filgrastim (12 fold increase in white blood cell count with appearance of myelocytes and myeloblasts ). In contrast patients without improvement were older than 60 years, had NYHA class III heart failure and experienced just 6-8 fold increases in leukocyte count. These factors are suggested to be predictors of clinical efficacy of G-CSF in patients with heart failure.
 ...
PMID:[Mobilization of bone marrow stem cells in the management of patients with heart failure. Protocol and first results of ROT FRONT trial]. 1289 Dec 52

Spinal neurosarcoidosis is rarely a presenting symptom. This case deals with a 45-year-old african woman who presented with a regressive spinal cord compression treated by parenteral corticosteroid. Different relapses allowed to diagnose multiple sclerosis. Spinal MRI scan showed diffuse enlargement of the cord with intense intramedullary enhancement from C3 to T1 and an aspect of large spinal cord from C7 to D1. Cranial MRI scan was normal. Radiographs and CT scan of the chest revealed an interstital syndrome without mediastinal lymphadenopathy (subgroup III). The serum angiotensin converting enzyme level was elevated in the blood as the cerebrospinal fluid. CSF fluid showed a lymphocytic meningitis. The bronchio-alveolar lavage found an hyperlymphocytosis with a high CD4/CD8 ratio. The neurological status and biological parameters were improved with oral corticotherapy treatment. This case report that a spinal cord involvement can reveal a sarcoidosis especially in the African race. Finally, in spite of lack of biopsy, the diagnosis is supported by clinical, biological and neuroradiological arguments.
 ...
PMID:[Sarcoidosis revealed by a spinal cord lesion]. 1510 71

We present a case of isolated cerebral neurosarcoidosis with remitting nodular lesions resembling intraventricular neoplasms. The patient, admitted at our Department for surgical treatment of a magnetic resonance imaging (MRI) demonstrated fourth ventricle lesion, presented acute intracranial hypertension. A second MRI performed before the scheduled operation showed the disappearance of the fourth ventricle lesion and a tetra-ventricular hydrocephalus. The patient has been treated with a third-ventriculostomy, followed, after 15 days, by ventriculoperitoneal shunt. High doses of steroids have been administered. Cerebrospinal fluid analysis has been conducted and a high concentration of ACE, specific marker of neurosarcoidosis, has been found. No biopsy was performed to avoid surgical complications. A systemic chemotherapy with azathioprine has been started, but the patient died six months later for worsening of the clinical conditions. The autopsy confirmed the diagnosis of neurosarcoidosis. This is the first MRI documented case of neurosarcoidosis with remitting lesions. Diagnosis of isolated neurosarcoidosis is difficult and it is based on clinical and radiological exclusion of other entities. CSF examination is useful for diagnosis, for the reported specificity and sensibility of ACE. Medical treatment is based on corticosteroids and chemotherapic agents. Neurosurgical intervention can be related to treat hydrocephalus due to ependymal and arachnoidal involvement or to remove large lesions. In our opinion biopsy should be limited only to ACE negative patients and to those who do not respond to chemotherapy.
 ...
PMID:Ghost lesions in patient with cerebral-isolated neurosarcoidosis. A case report. 1655 96


<< Previous 1 2 3 4 Next >>