Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although monogenic diseases often show extreme clinical phenotypes, the major burden of genetic ill health lies in the more prevalent polygenic disorders, such as diabetes, hypertension and multiple sclerosis. These conditions affect many thousands of individuals and their management consumes vast amounts of health care resources: in the UK some 80,000 people have multiple sclerosis; the estimated financial cost to society of introducing treatments, such as beta interferon, could be as high as 250 million pounds per year. Knowledge on the genetics of these common diseases is poor, but has potentially received a considerable boost with the arrival of whole genome screening. The genome screen in insulin-dependent diabetes mellitus (IDDM) reported in 1994 was the first in a human polygenic disease. Since this publication, whole genome screening has been performed in a variety of human polygenic diseases, including schizophrenia, bipolar affective disorder, non-insulin-dependent diabetes mellitus (NIDDM), inflammatory bowel disease, asthma and multiple sclerosis.
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PMID:The genetic analysis of multiple sclerosis. 919 29

We present an 86-years-old woman's case with paralysis in her left hand of abrupt apparition, accompanied by arterial hypertension and dizziness. The investigation revealed erythrocytosis, leukocytosis, thrombocytosis, with normal arterial O2 saturation (O2 SAT), increased of his red cell volume and blood viscosity. The polycythaemia vera (PV) was diagnose and the paralysis disappeared, when 24 hours before a phlebotomy was practiced, and the function was recovered by the hand. We analysed the presents diagnostics criteria of the disease defined by Polycythaemia Vera Study Group (PVSG). The different treatments for PV are discussed; in addition to venesection, conventional treatment include chemotherapy with hydroxyurea and pipobroman, as well as the erythropheresis, -interferon and aspirin. All of the treatments are associated with complications; thrombotic in the case of phlebotomy; malignancies and gastrointestinal bleeding in the case of myelosuppressive treatments and aspirin. We think the optimal treatment for PV is a judicious combination of the available alternatives, depending on the phase of the disease, and the age of the patient.
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PMID:[Primary polycythaemia vera in the elderly]. 958 Jan 77

Renal cell carcinoma (RCC) continues to be a frustrating tumor for clinicians to manage and treat. Progress has been made in the identification of risk factors, particularly dietary risk factors. An increased risk has been seen with frequent consumption of fried meat and poultry. Citrus fruits, vitamin C, beta-carotene, and alpha-tocopherol have demonstrated a protective effect against RCC. Other factors that have been associated with the risk of RCC are smoking (which doubles the risk), obesity, hypertension, and exposure to asbestos and petroleum products. Response rates for systemic treatment of RCC continue to hover at about 20%; however, some nonchemotherapy treatments may provide palliation with few side effects. In addition, lower dose combinations of interleukin-2 and interferon alfa may be as beneficial as higher dose regimens, but with less toxicity. Molecular prognostic factors, including proliferation markers, karyometric analyses, oncogenes, and cell adhesion molecules and proteases are areas of intense investigation and may provide mechanisms for identifying patients who require more (or less) aggressive treatment.
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PMID:Renal cell carcinoma. 961 63

-Apoptosis has been reported to play a pivotal role in vascular remodeling. However, cellular mechanisms of apoptosis in vascular smooth muscle cells (VSMCs) have not been well defined. In this study, we focused on interleukin-1beta-converting enzyme (ICE), a key protease in the induction of apoptosis in lymphocytes and fibroblasts. We observed an increase in ICE mRNA expression in rat aortic VSMCs after serum depletion, with a peak at 12 hours and then a gradual decline. This was associated with DNA fragmentation, a hallmark of apoptosis and morphological changes of apoptosis. Treatment of these VSMCs with the ICE inhibitor N-(N-acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic acid (YVAD-CHO) attenuated DNA fragmentation. The increased ICE mRNA expression was preceded by an increase in the mRNA expression of interferon regulatory factor (IRF)-1, peaking at 6 hours after serum removal, and a rapid but transient decrease in IRF-2 mRNA expression, reaching a nadir at 3 hours after serum depletion. To demonstrate that these reciprocal changes in IRF-1 and IRF-2 regulated ICE expression and induced apoptosis, we transfected antisense oligonucleotides for IRF-1 and IRF-2 into VSMCs and examined ICE mRNA expression and apoptotic changes. IRF-1 antisense pretreatment attenuated the increase in ICE expression and reduced apoptotic changes, whereas IRF-2 antisense treatment increased ICE mRNA expression and enhanced apoptotic changes. Taken together, our results suggest that serum growth factor depletion in VSMCs upregulates IRF-1 and downregulates IRF-2, thereby increasing ICE expression and inducing apoptosis.
Hypertension 1999 Jan
PMID:Interferon regulatory factors regulate interleukin-1beta-converting enzyme expression and apoptosis in vascular smooth muscle cells. 993 Oct 97

Angiotensin (Ang) II stimulates proliferation of vascular smooth muscle cells (VSMC) via its specific receptor AT1 subtype, possibly leading to atherosclerosis in hypertension. On the other hand, a cytokine interferon (IFN)-gamma has been shown to have an anti-atherosclerotic effect. In the present study, we examined a possible role of IFN-gamma in AT1 receptor gene regulation in VSMC. A firefly luciferase expression vector driven by the rat AT1a receptor gene promoter ( approximately 3.2 kb) was transfected into the cultured rat VSMC, and luciferase expression was determined to estimate the transcription function of the AT1a receptor gene promoter. RT-PCR was also carried out to determine mRNA expression of AT1a receptor in VSMC. IFN-gamma treatment decreased AT1a receptor mRNA expression as well as luciferase expression in a dose-dependent manner. The analysis with deletion DNA fragments showed that the IFN-responsive element was located between -987 and -331 positions, where multiple GAS (gamma interferon activated site)-like elements were identified. The expression suppression was reversed by either a MAPKK inhibitor PD98059 or a Jak-2 inhibitor AG-490. These results suggest that IFN-gamma can inhibit AT1 receptor expression at gene transcription level, and that the transcription suppression is dependent on MAP kinase and Jak-2. Inhibition of AT1a receptor expression may possibly be implicated in the anti-atherosclerotic action of IFN-gamma in VSMC.
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PMID:Transcriptional suppression of rat angiotensin AT1a receptor gene expression by interferon-gamma in vascular smooth muscle cells. 1046 2

A 58-year-old man had long-standing lesions of presumed large plaque parapsoriasis. Following treatment for nodal Hodgkin's disease (HD), these became more infiltrated, with a diagnosis of mycosis fungoides (MF). A few months later, nodules appeared on the right leg, which was lymphoedematous after inguinal irradiation for HD. Histopathological examination showed CD3+, CD30-, CD15- large pleomorphic lymphocytes, leading to the diagnosis of transformed MF. The cutaneous lesions were successfully treated with topical nitrogen mustard and interferon alfa-2b then methotrexate, but his general health worsened with depression and malaise, without specific neurological symptoms or extracutaneous spreading of the lymphoma. Cerebral computed tomographic scan revealed a cerebellar subdural collection, arachnoid cyst and quadriventricular hydrocephaly, initially considered to be non-specific. After a few weeks, clinical symptoms of intracranial hypertension appeared, and a cerebrospinal fluid (CSF) examination revealed meningeal involvement by the lymphoma. These cells were CD3-negative and the diagnosis was confirmed by polymerase chain reaction (PCR) study, which revealed an identical clonal rearrangement of the T-cell receptor gamma gene between cutaneous biopsies and the CSF. Repeated intrathecal injections of methotrexate and cranial irradiation were performed and the patient was still alive after 13 months. This case illustrates the possible meningeal involvement of MF that may be preceded by atypical and mild neurological or psychiatric symptoms, which may be dissociated from the evolution of the cutaneous lesions. Moreover, PCR study may be useful for both diagnosis and monitoring.
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PMID:Meningeal involvement by a transformed mycosis fungoides following Hodgkin's disease. 1058 78

We report here a patient who suffered from PCR- confirmed human herpesvirus type 6 (HHV-6) meningoencephalitis after allogeneic purified CD34+ cell transplantation from his HLA-mismatched sibling donor, even though he had been on intense prophylaxis with i.v. ganciclovir (GCV), acyclovir (ACV) and gamma-globulin containing a specific antibody against HHV-6. Serological evaluation disclosed that both the donor and recipient had IgG antibody against HHV-6 before transplantation. His blood WBC count started to transiently increase on day 10, and all blood components had decreased by day 20. He then developed a severe headache and high blood pressure, and sporadic abnormal neurological findings including nystagmus and delirium. An analysis of cerebrospinal fluid (CSF) revealed 8 cells/microl, a glucose level of 130 mg/dl and a protein level of 201 mg/dl (normal, 50 mg/dl) on day 26. At the time, HHV-6 was detected only in CSF by a PCR-based method and he was diagnosed as having meningoencephalitis due to the local reactivation of HHV-6. Although he failed to respond to high-dose therapy with ACV (60 mg/kg/day) and gamma-globulin, the DNA of this virus disappeared from the CNS upon treatment with GCV (30 mg/kg/day) combined with the intraventricular infusion of alpha-interferon. His clinical course was further complicated with meningoencephalitis due to staphylococcus epidermidis, and he died of tentorial herniation on day 79 without the recovery of blood components. This experience may indicate that intense prophylaxis to prevent reactivation of HHV-6 in the CNS is essential for the management of such profoundly immunosuppressed patients.
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PMID:HLA-mismatched CD34-selected stem cell transplant complicated by HHV-6 reactivation in the central nervous system. 1074 66

Cryoglobulins are immunoglobulins that persist in serum, precipitate with cold temperature, and resolve when rewarmed. Cryoglobulinemia are part of systemic vasculitis, and they are in the subgroup of immune complex type vasculitis. Mixed cryoglobulinemia are associated with malignant B lymphoproliferative disorders, auto-immune and chronic infectious diseases, particularly hepatitis C virus infection. Mixed cryoglobulinaemia has a variable prognosis, depending mainly on renal involvement, systemic extension, and severity of hypertension. In pilot studies, alpha interferon seemed promising to treat symptomatic mixed cryoglobulinemia, because of its immunomodulating and antiviral properties. In severe or resistant forms of mixed cryoglobulinemia, plasmapheresis or immunosuppressive agents may be useful.
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PMID:[Mixed cryoglobulinemia]. 1192 52

Angiotensin II type 2 (AT2) receptor is developmentally regulated and exerts antiproliferative and proapoptotic actions. Genetic ablation of this receptor in mice affects regulation of blood pressure, but the involvement of the AT2 receptor in the pathogenesis of hypertension remains unknown. In the present study, we examined developmental changes of angiotensin receptor subtypes in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP), and compared them with those in normotensive Wistar-Kyoto rats (WKY). We also investigated the regulation and functional role of the AT2 receptor in cultured mesangial cells. Receptor binding and Northern blot analyses revealed that AT2 receptor expression is significantly lower in the SHRSP kidney than in the WKY kidney during the perinatal period, while AT1 receptor expression is not different between them. In WKY mesangial cells, AT2 receptor stimulation exerted a potent antiproliferative effect; this effect was not observed in SHRSP cells lacking the AT2 receptor expression. The expression of interferon regulatory factor (IRF)-1 paralleled the growth-dependent induction of AT2 receptor in WKY mesangial cells, and transfection of IRF-1 antisense oligonucleotide significantly suppressed AT2 receptor expression, indicating IRF-1-dependent regulation of AT2 receptor expression in mesangial cells. However, this induction was inefficient in SHRSP cells. Thus, we found impaired AT2 receptor expression in the SHRSP kidney in vivo and in mesangial cells in vitro. The unbalanced expression of renal angiotensin receptor subtypes with exaggerated AT1 receptor signaling during early life in SHRSP may play a role in the programming for hypertension and related renal injury.
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PMID:Expression and role of angiotensin II type 2 receptor in the kidney and mesangial cells of spontaneously hypertensive rats. 1192 18

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of primary pulmonary hypertension characterized by thin-walled microvessels infiltrating the peribronchial and perivascular interstitium, the lung parenchyma, and the pleura. These proliferating microvessels are prone to bleeding, resulting in accumulation of hemosiderin-laden macrophages in alveolar spaces. Here we report 2 cases of PCH with pulmonary hypertension, 1 of them associated with mechanical intravascular hemolysis, a feature previously reported in other hemangiomatous diseases, but not in PCH. Case 2 was diagnosed by pulmonary biopsy; to our knowledge the patient is the second adult to be treated with interferon alpha-2a. Review of the literature identified 35 patients with PCH and pulmonary hypertension. The prognosis is poor and median survival was 3 years from the first clinical manifestation. Dyspnea and right heart failure are the most common findings of the disease. Hemoptysis, pleural effusion, acropachy, and signs of pulmonary capillary hypertension are less common. Chest X-ray or computed tomography scan usually shows evidence of interstitial infiltrates, pulmonary nodules, or pleural effusion. Hemodynamic features include normal wedge pressures. Radiologic and hemodynamic findings are undifferentiated from those of pulmonary veno-occlusive disease but differ from other causes of primary pulmonary hypertension. Epoprostenol therapy, considered the treatment of choice in patients with primary pulmonary hypertension, may produce pulmonary edema and is contraindicated in patients with PCH. Regression of lesions was reported in 1 patient treated with interferon therapy and 2 other patients stabilized, including our second patient. PCH was treated successfully by lung transplantation in 5 cases. Early recognition of PCH in patients with suspected primary pulmonary hypertension is possible based on clinical and radiologic characteristics. Diagnosis by pulmonary biopsy is essential for allowing appropriate treatment.
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PMID:Pulmonary capillary hemangiomatosis associated with primary pulmonary hypertension: report of 2 new cases and review of 35 cases from the literature. 1244 98


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