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)

Voltage-gated calcium channels are key sources of calcium entry into the cytosol. Mutations in calcium channels have been implicated in numerous disorders such as migraine, incomplete congenital X-linked stationary night blindness, epilepsy, and ataxia, and they are important therapeutic targets for the treatment of pain, stroke, hypertension, and epilepsy. Calcium channel antagonists can be broadly classified into three groups. 1) Inorganic ions typically nonselectively block the pore of most calcium channel subtypes, and in some cases, alter gating kinetics. 2) Peptides isolated from arachnids, cone snails, and snakes frequently selectively antagonize individual calcium channel subtypes by direct occlusion of the pore or altering gating kinetics. 3) Small organic molecules of various structure-activity-relationship (SAR) classes can mediate both selective and nonselective effects on individual calcium channel subtypes, and occlude the pore or reduce channel availability. Here, we provide an overview of classes of inhibitors of non-L-type calcium channels.
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PMID:Molecular pharmacology of non-L-type calcium channels. 1597 66

The clinical, hemodynamic, and pathologic features of hypertensive encephalopathy in two cats with reduced renal mass are described. The cats developed a progressive syndrome of lethargy, ataxia, blindness, stupor, and seizures following an abrupt increase in blood pressure associated with a surgical reduction in renal mass. The cats had severe gross brain edema, evidenced by cerebellar changes of caudal coning and cranial displacement over the corpora quadrigemina and cerebral changes of widening and flattening of the gyri. Histologically, interstitial edema was most pronounced in the cerebral white matter. Hypertensive vascular lesions were present as hyaline arteriolosclerosis in one cat and hyperplastic arteriolosclerosis in the other. Rare foci of parenchymal microhemorrhages and necrosis were also observed. Systemic hypertension (especially severe or rapidly developing) accompanied by neurologic signs and the pathologic findings of diffuse brain edema with cerebral arteriolosclerosis are consistent with an etiologic diagnosis of hypertensive encephalopathy.
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PMID:Hypertensive encephalopathy in cats with reduced renal function. 1614 10

We report 6 patients with Cheiro-oral syndrome (COS), with special reference to clinical features and responsible lesions. The time intervals from the onset of symptoms to arrival in our department were less than 24 hours in 3 patients, 2 days in 2, and 5 days in 1. All patients had subjective sensory disturbance involving the unilateral hand and ipsilateral perioral regions, and 4 patients presented with objective sensory disturbance. The body parts of tingling sensation tended to be larger than those of superficial sensory disturbance. Three patients developed motor disturbance including hemiparesis with or without ataxia, clumsiness of fine finger movements, and dysarthria. Magnetic resonance imaging revealed fresh infarctions around the thalamus, including lacunar infarctions in 5 patients and branch atheromatous disease in 1 patient. The lesion sites responsible for COS were ventral posterolateral (VPL) and ventral posteromedial (VPM) nuclei in the thalamus in 4 patients, thalamic pulvinar nucleus and medial geniculate body in 1, thalamic ventroposterior region-internal capsule-corona radiata in 1. Three patients had asymptomatic brain infarctions. Risk factors were hyperlipidemia, hypertension, diabetes mellitus, smoking, arteriosclerosis of the carotid artery, and polycythemia. In the convalescent stage, 5 patients suffered from residual sensory-motor disturbance, whereas 1 patient recovered from COS. COS has been attributed mainly to small infarctions in the thalamic ventroposterior nuclei. However, it is suggested that damage to ascending sensory fibers projecting to the thalamic VPL and VPM nuclei can cause COS. Because initial symptoms of COS are apt to be overlooked, early diagnosis and treatment are necessary to avoid residual sensory-motor disturbance.
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PMID:[A clinicoanatomical study of thalamic cheiro-oral syndrome]. 1652 19

Uteroplacental insufficiency (UPI) leads to intrauterine growth restriction (IUGR), which predisposes infants toward renal insufficiency early in life and increases the risk of kidney-related adult morbidities, such as hypertension. This compromised in utero environment has been demonstrated to impair nephrogenesis, as evidenced by a reduced nephron endowment in humans and in rats rendered IUGR by UPI. Concordantly, we have observed that IUGR rats have increased kidney p53 protein levels associated with increased apoptosis. Several factors can regulate p53 gene expression and activity, including posttranslational modifications and protein-protein interactions in the cell. Among these, two important mechanisms are 1) phosphorylation of the amino terminal serine 15 [phospho-p53 (Ser15)], which increases p53 stability and apoptotic activity, and 2) the murine double-minute (MDM2) functional circuit that limits further p53-induced apoptosis by promoting proteosomal degradation of p53. We hypothesize that UPI induces an increase in phospho-p53 (Ser15) in association with an absent MDM2 response, predisposing the kidney to increased apoptosis. To test our hypothesis, we induced IUGR through bilateral uterine artery ligation of the pregnant rat. UPI significantly increased phospho-p53 (Ser15), as well as ataxia teleangiectasia-mutated kinase/A-T-related kinase and dsDNA-activated protein kinase kinase levels, which induce phosphorylation of p53. In contrast, UPI induced no increase in kidney MDM2 mRNA and protein levels in IUGR pups. We conclude that among multiple mechanisms that affect nephrogenesis, UPI induces an increase in p53 phosphorylation without a corresponding increase in MDM2 expression, and we speculate that this response may contribute to the increased apoptosis previously described in the IUGR kidney.
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PMID:Uteroplacental insufficiency increases p53 phosphorylation without triggering the p53-MDM2 functional circuit response in the IUGR rat kidney. 1691 26

This report is about a rare case of a lumbar spinal dural arteriovenous fistula (DAVF) with distant brainstem symptoms of vertigo and ataxia. Brain magnetic resonance imaging (MRI) demonstrated a high signal abnormality in the lower pons, medulla, and cervico-medullary junction, presumably related to venous hypertension. Spinal MRI revealed markedly dilated veins along the dorsal aspect of the cord, while spinal angiography confirmed the presence of a lumbar spinal DAVF. Because lumbar DAVF may cause remote brainstem symptoms, spinal DAVF should be considered in the differential diagnosis of high signal MRI abnormalities localized in the brainstem. Properly extending the scanning range is essential in the diagnosis.
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PMID:Lumbar spinal dural arteriovenous fistula presenting with brainstem symptomatology: A case report. 1695 Jul 13

There are multiple reports in the literature of serious and at times fatal complications after cervical spine manipulation therapy (CSMT), even though CSMT is considered by some health providers to be an effective and safe therapeutic procedure for head and neck pain syndromes. We report a case of a young female with cervicalgia and headache with fatal posterior circulation cerebrovascular accident after CSMT. Serious complications are infrequent, with a reported incidence between one per 100,000 to one in 2 million manipulations. The most frequent injuries involve artery dissection or spasm. Stroke as a complication of cervical manipulation and dissection of the vertebral arteries (VAD) is a rare but well recognized problem. Neck pain, headache, vertigo, vomiting and ataxia are typical symptoms of VAD, but this vascular injury also can be asymptomatic. The most common risk factors are migraine, hypertension, oral contraceptive pills and smoking. Stroke following CSMT is more common than the literature reports. The best values derive from retrospective surveys. The lack of identifiable risk factors place those who undergo CSMT at risk of neurologic damage. Accurate patient information and early recognition of the symptoms are important to avoid catastrophic consequences.
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PMID:Cervical spine manipulation: an alternative medical procedure with potentially fatal complications. 1845 37

Meckel syndrome (MKS) is a rare lethal autosomal recessive disorder characterized by the presence of occipital encephalocele, cystic kidneys, fibrotic changes of the liver and polydactyly. Joubert syndrome (JS)-related disorders (JSRDs) or cerebello-oculo-renal syndromes (CORS) are a group of recessively inherited conditions characterized by a molar tooth sign (MTS) on cranial MRI, a set of core clinical features (developmental delay/mental retardation, hypotonia, ataxia, episodic breathing abnormalities, abnormal eye movements) and variable involvement of other systems including renal, ocular, central nervous system, craniofacial, hepatic, and skeletal. A significant clinical overlap between MKS and JSRD/CORS has been recognized in the literature. We describe a group of 10 Hutterite patients, of which 7 had been previously diagnosed with MKS, with a JSRD. Clinical features include variable early mortality, cognitive handicap, a characteristic dysmorphic facial appearance, hypotonia, ataxia, abnormal breathing pattern, nystagmus, and MTS on MRI. Additional features include occipital encephalocele, posterior fossa fluid collections resembling Dandy-Walker malformation, hydrocephalus, coloboma, and renal disease. This JSRD is a recognizable dysmorphic syndrome characterized by hypertelorism, deep-set eyes, down-slanting palpebral fissures, ptosis, arched eyebrows with medial sparseness, square nasal tip, short philtrum with tented upper lip, open mouth with down-turned corners, and posteriorly rotated low-set ears. Renal disease is present in 70% of patients and is characterized by cystic kidneys, abnormalities in renal function and hypertension. Homozygous deletions of NPHP1 and the known loci for JS/JSRD and MKS were excluded by identity-by-descent mapping studies suggesting that this condition in the Hutterites represents yet another locus for a JSRD.
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PMID:Meckel syndrome in the Hutterite population is actually a Joubert-related cerebello-oculo-renal syndrome. 1760 1

The plasma membrane calcium ATPase (PMCA) uses energy to pump calcium (Ca2+) ions out of the cytosol into the extracellular milieu, usually against a strong chemical gradient. This energy expenditure is necessary to maintain a relatively low intracellular net Ca2+ load. Mammals have four genes (ATP2B1-ATP2B4), encoding the proteins PMCA1 through PMCA4. Transcripts from each of these genes are alternatively spliced to generate several variant proteins that are in turn post-translationally modified in a variety of ways. Expressed ubiquitously and with some level of functional redundancy in most vital tissues, only one of the four genes--Atp2b2--has been causally linked through naturally occuring mutations to disease in mammals: specifically to deafness and ataxia in spontaneous mouse mutants. In humans, a missense amino acid substitution in PMCA2 modifies the severity of hearing loss. Targeted null mutations of the Atp2b1 and Atp2b4 genes in mouse are embryonic lethal and cause a sperm motility defect, respectively. These phenotypes point to complex human diseases like hearing loss, cardiac function and infertility. Changes in PMCA expression are associated with other diseases including cataract formation, carciniogenesis, diabetes, and cardiac hypertension and hypertrophy. Severity of these diseases may be affected by subtle changes in expression of the PMCA isoforms expressed in those tissues.
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PMID:The plasma membrane calcium ATPase and disease. 1819 44

Fragile X-associated tremor/ataxia syndrome (FXTAS) is generally considered to be uncommon in older female carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene; however, neither prevalence, nor the nature of the clinical phenotype, has been well characterized in female carriers. In this study, we evaluated 146 female carriers (mean, 42.3 years; range, 20-75 years) with and without core features of FXTAS (tremor; gait ataxia), and 69 age-matched controls (mean, 45.8 years; range, 21-78 years). Compared with controls, carriers with definite or probable FXTAS had greater medical co-morbidity, with increased prevalence of thyroid disease (P = 0.0096), hypertension (P = 0.0020), seizures (P = 0.0077), peripheral neuropathy (P = 0.0040), and fibromyalgia (P = 0.0097), in addition to the typical symptoms of FXTAS-tremor (P < 0.0001) and ataxia (P < 0.0001). The non-FXTAS premutation group had more complaints of chronic muscle pain (P = 0.0097), persistent paraesthesias in extremities (P < 0.0001), and history of tremor (P < 0.0123) than controls. The spectrum of clinical involvement in female carriers with FXTAS is quite broad, encompassing a number of medical co-morbidities as well as the core movement disorder. The remarkable degree of thyroid dysfunction (17% in the non-FXTAS group and 50% in the FXTAS group) warrants consideration of thyroid function studies in all female premutation carriers, particularly those with core features of FXTAS.
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PMID:Expanded clinical phenotype of women with the FMR1 premutation. 1834 75

The cerebellum has almost never been considered responsible for conjugate deviation of the eyes (CDE). A few cases of CDE caused by cerebellar lesions without the involvement of the brainstem have been reported, but the lesions were too large to evaluate their localization in the cerebellum. In this report, we describe 2 cases of isolated CDE caused by small cerebellar vascular lesions and a case of CDE and staggering gait that occurred following cerebellar infarction. We further describe cases of head rotation without CDE and those of vertigo without CDE or head rotation due to a similar small lesion. Case 1: A 73-year-old woman with rheumatism was brought to our department because of sudden-onset of difficulty in looking to the right. She was admitted 3 hours after onset; at admission she was alert and well-oriented and denied both vertigo and nausea. Neurologic examination revealed CDE to the left; however, no limb ataxia was detected. Diffusion-weighted MRI showed a small infarction in the white matter of the right PICA area near the vermis. Her CDE disappeared spontaneously within 2 days. Case 2: A 79-year-old man with hypertension exhibited CDE to the right without vertigo or ataxia following a small hemorrhage in the cerebellan area mentioned in Case 1. Case 3: A 65-year-old man with hypertension presented with CDE to the right and staggering gait after a small infarction in an area lateral to that mentioned above. The first 2 cases suggest that a small cerebellar vascular lesion can produce isolated CDE to the side contralateral to the lesion. The region responsible for CDE in these cases was located in the white matter of the PICA area near the vermis, although similar lesions in Cases 4 and 5 produced no CDE.
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PMID:[Small cerebellar vascular lesion can produce isolated conjugate deviation of the eyes]. 1856 61


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