Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Restrictive dermopathy is a rare, fatal, autosomal recessive, congenital skin disease. Rigidity of translucent thin skin, which is thus highly vulnerable and tears, spontaneously causes intra-uterine fetal akinesia or hypokinesia deformation sequence (FADS), characteristic dysmorphic facies with fixed open mouth in O position, and generalized joint contractures (arthrogryposis). Polyhydramnios and pulmonary hypoplasia are distinctive manifestations, leading to respiratory insufficiency and premature delivery at about 31 weeks of gestation. We report on a case of a prematurely born infant who presented with the typical morphological features and describe the light- and electron-microscopical findings as described in the literature.
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PMID:[Restrictive dermopathy]. 1059 57

Pathophysiological mechanisms of major symptoms of Parkinson's disease are discussed from experiences of stereotaxic surgery. Tremor completely disappears by a lesion in the ventral intermediate nucleus(Vim) which receives proprioceptive sense from the periphery. Rigidity is alleviated by a lesion in the globus pallidus(GP) and the ventral lateral nucleus(VL) equally. Since GP projects to the prefrontal motor cortex via VL, surgery to either of those structures causes the same result. Akinesia is classified into three types: secondary akinesia, primary akinesia, and akinesia due to psychomotor dysfunction. Gradual spread of neuronal degeneration within the substantia nigra pars compacta may explain the progression of akinesia. Psychological or psychiatric disorder becomes major symptom in the late stage. Posteroventral pallidotomy may change emotional state in some cases by influencing the limbic motor circuit.
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PMID:[Clinical pathophysiology of parkinsonian symptoms: from experiences of stereotaxic surgery]. 1106 35

Pallidotomy has recently regained acceptance as an effective treatment for Parkinson's disease. From our 50 cases of unilateral pallidotomy and 10 cases of staged bilateral pallidotomy, details and indications of the procedure is described. The unilateral pallidotomy is quite effective for L-dopa induced dyskinesia, which usually completely disappears soon after the operation. The effect is long-lasting. When on-off phenomenon exists, unilateral pallidotomy improves off-stage rigidity or akinesia. Symptoms during on-stage are not changed. Indications of pallidotomy is that(1) L-dopa induced dyskinesia, and(2) on-off phenomenon. Bilateral pallidotomy, even by staged one, causes severe drooling, or speech disturbance(the volume of the voice decreases and the articulation worsens), and is not recommended. Vim thalamotomy is, on the other hand, the established treatment for tremor of Parkinson's disease or of essential tremor. The effect is long-lasting. Rigidity or akinesia is not expected to be improved so much.
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PMID:[Details and indications of pallidotomy and thalamotomy for Parkinson's disease]. 1106 49

We report a 56-year-old woman with progressive gait disturbance. Her mother had Parkinson's disease with onset at age 70. She died at age 74 and the post-mortem examination confirmed the diagnosis of Lewy body positive Parkinson's disease. The patient was well until the age of 50(1995) when she noted an onset of resting tremor and difficulty of gait. She also developed delusional ideation and was admitted to a psychiatric service of another hospital, where a major tranquilizer was given. The delusion disappeared but she developed marked rigidity. The major tranquilizer was discontinued and an anticholinergic and amantadine HCl were given. She showed marked improvement to Hoehn and Yahr stage II and was discharged. In 1995, when she was 52 years of the age, she developed delusion again and a major tranquilizer was given. She developed marked parkinsonism again and became Hoehn and Yahr stage V. The major tranquilizer was discontinued and she was treated with levodopa/carbidopa, trihexyphenidyl, bromocriptine, and dops. She improved remarkably to stage II. She was admitted to our service on October 8, 1996 for drug adjustment. She was alert and not demented. She was anxious but delusion or hallucination was noted. Higher cerebral functions were intact. Cranial nerve functions were also intact except for masked face and small voice. Her posture was stooped and steps were small. She showed retropulsion and moderate bradykinesia. Resting tremor was noted in her left hand. Rigidity was noted in both legs. No cerebellar ataxia or weakness was noted. Deep tendon reflexes were within normal range and sensation was intact. Her cranial MRI revealed some atrophic changes in the putamen, in which a T 2-high signal linear lesion was seen along the lateral border of the putamen bilaterally. In addition, posterior part of the putamen showed T 2-low signal intensity change. She was treated with 1.6 mg of talipexole, 6 mg of trihexyphenidyl, and 100 mg of L-dops. She was in stage III of Hoehn and Yahr. She developed neurogenic bladder with a large amount of residual urine for which she required catheterization. She was transferred to another hospital. Despite drug adjustment, she lost response to levodopa and her parkinsonism deteriorated gradually. She also developed syncope orthostatic hypotension. In April of 1998, she developed intracerebral hemorrhage and was admitted again on April 19, 1998. She was unable to stand and showed marked akinesia and rigidity. She was in stage V of Hoehn and Yahr. Her cranial CT scan revealed bilateral high-density lesions in the posterior parietal lobes. She developed dysphagia for which she required gastrostomy. She was transferred to another hospital but her clinical condition deteriorated further. On December 22, 1999, she developed fever and dyspnea and was admitted to our service again. She developed cardial arrest at the emergency room from hypoxia. She was resuscitated; however, she was comatose with loss of brain stem reflexes. Later on she developed generalized myoclonus. She developed cardiac arrest and pronounced dead on December 28, 1999. The patient was discussed in a neurological CPC. The chief discussant arrived at the conclusion that the patient had striatonigral degeneration because of poor response to levodopa in the later course, autonomic failures, and MRI changes. Some other participants thought that the patient had a form of familial Parkinson's disease. Opinions were divided into these two possibilities. Post-mortem examination revealed that the substantia nigra showed intense neuronal loss and gliosis, however, no Lewy bodies were seen. In addition, intracytoplasmic inclusions were seen in oligodendrocytes. The putamen was markedly atrophic in its posterior part with marked gliosis and neuronal loss. The ventromedial part of the pontine nucleus also showed neuronal loss and intracytoplasmic glial inclusions. Pathologic diagnosis was multiple system atrophy. In the parietal lobe, an arteriovenous malformation with bleeding was noted. This is very unique case. Although her mother had Lewy body-positive Parkinson's disease, the patient had Lewy body-negative multiple system atrophy with a-synuclein-positive glial inclusions. Whether this is just a coincidental occurrence or the presence of a genetic load for Parkinson's disease might triggered her multiple system atrophy is an interesting question to be answered in future.
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PMID:[A-56-year-old woman with parkinsonism, whose mother had Parkinson's disease]. 1142 77

The aim of the present study was to examine a potential beneficial effect of the blockade of metabotropic glutamate receptor subtype 5 (mGluR5) by the selective non-competitive antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), in models of parkinsonian symptoms in rats. Haloperidol, 0.25, 0.5 and 1mg/kg ip, was used to induce hypolocomotion, catalepsy and muscle rigidity, respectively. The locomotor activity was estimated by an open-field test, the catalepsy -- by a 9-cm cork test. The muscle rigidity was measured as an increased resistance of a hind leg to passive extension and flexion at the ankle joint. Additionally, increases in the electromyographic activity were recorded in the gastrocnemius and tibialis anterior muscles. MPEP (1.0-10mg/kg ip) inhibited the muscle rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alone (5mg/kg ip) did not induce catalepsy, nor did it influence the muscle tone or locomotor activity in rats. The present results suggest that blockade of mGluR5 receptors may be important to amelioration of both parkinsonian akinesia and muscle rigidity.
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PMID:Blockade of the metabotropic glutamate receptor subtype 5 (mGluR5) produces antiparkinsonian-like effects in rats. 1154 61

Primary motor cortex (MI) neurons discharge vigorously during voluntary movement. A cardinal symptom of Parkinson's disease (PD) is poverty of movement (akinesia). Current models of PD thus hypothesize that increased inhibitory pallidal output reduces firing rates in frontal cortex, including MI, resulting in akinesia and muscle rigidity. We recorded the simultaneous spontaneous discharge of several neurons in the arm-related area of MI of two monkeys and in the globus pallidus (GP) of one of the two. Accelerometers were fastened to the forelimbs to detect movement, and surface electromyograms were recorded from the contralateral arm of one monkey. The recordings were conducted before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rendering the animals severely akinetic and rigid with little or no tremor. The mean spontaneous MI rates during periods of immobility (four to five spikes/sec) did not change after MPTP; however, in this parkinsonian state, MI neurons discharged in long bursts (sometimes >2 sec long). These bursts were synchronized across many cells but failed to elicit detectable movement, indicating that even robust synchronous MI discharge need not result in movement. These synchronized population bursts were absent from the GP and were on a larger timescale than oscillatory synchrony found in the GP of tremulous MPTP primates, suggesting that MI parkinsonian synchrony arises independently of basal ganglia dynamics. After MPTP, MI neurons responded more vigorously and with less specificity to passive limb movement. Abnormal MI firing patterns and synchronization, rather than reduced firing rates, may underlie PD akinesia and persistent muscle rigidity.
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PMID:Enhanced synchrony among primary motor cortex neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. 1204 70

Specific degeneration of the nigrostriatal dopamine (DA) neurons of the substantia nigra pars compacta and the resulting loss of nerve terminals accompanied by DA deficiency in the striatum are responsible for most of the movement disturbances called parkinsonism, i.e., muscle rigidity, akinesia, and resting tremor, observed in Parkinson's disease (PD). We and other workers have found changes in the levels of cytokines, neurotrophins, and other apoptosis-related factors in the nigro-striatal region of postmortem brain and/or in the cerebrospinal fluid (CSF) from PD patients, or from animal models of PD such as 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP)-induced PD in mice or 6-hydroxydopamine (6-OHDA)-induced PD in rats. The most remarkable changes observed specifically in the nigrostriatal region were decreased levels of neurotrophins supporting DA neurons. These results indicate that the process of cell death in the nigrostriatal DA neurons in PD may be the so-called programmed cell death, i.e., apoptosis. Thus gene therapy for PD should aim both at supplementing the decreased striatal DA level by introducing the genes of DA-synthesizing enzymes into non-DA cells in the striatum and at supporting or restoring DA neurons by preventing apoptosis by introducing genes that block the process of apoptosis.
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PMID:Parkinson's disease: changes in apoptosis-related factors suggesting possible gene therapy. 1211 64

A potent heteronymous excitation of quadriceps motoneurones via common peroneal group II afferents has recently been demonstrated in normal subjects. The aim of this study was to investigate whether this group II excitation contributes to rigidity in Parkinson's disease. The early and late facilitations of the quadriceps H reflex elicited by a conditioning volley to the common peroneal nerve (CPN) at twice motor threshold, attributed to non-monosynaptic group I and group II excitations, respectively, were investigated. The comparison was drawn between results obtained in 20 "de novo" patients with Parkinson's disease (hemiparkinsonian, 17; bilateral, three) and 20 age-matched normal subjects. There was no statistically significant effect of "group" (patients/controls), "duration", "global severity" [Unified Parkinson's Disease Rating Scale (UPDRS)] or "side" (unilaterally versus bilaterally affected) factors on either group I or group II facilitations. To further the analysis, the factors of status (affected or non-affected limb), akinesia (lower limb akinesia score) and rigidity (lower limb rigidity score) were entered in a general linear model to explain the variations of the quadriceps H reflex facilitation. Rigidity was the only factor useful in predicting the value of the group II facilitation of the quadriceps H reflex (P < 0.007). Group I and group II facilitation was then compared between the rigid, non-rigid and control lower limbs [multivariate analysis of variance (MANOVA)]. Results are represented as mean +/- SEM (standard error of the mean). Group II facilitation was enhanced in the rigid lower limb of unilaterally affected patients (153.2 +/- 7% of control H reflex) compared with non-rigid lower limbs (124 +/- 4% of control H reflex; P < 0.007) or control lower limbs (126.1 +/- 4.1%; P < 0.01). There was no difference between the non-rigid lower limbs of the unilaterally affected patients and the control lower limbs, but a difference was observed between the rigid lower limbs of unilaterally less affected and bilaterally more affected patients (153.2 +/- 7% and 123.8 +/- 7.5% of control H reflex, respectively; P < 0.04). These results suggest a facilitation of the transmission in the interneuronal pathway activated by group II afferents in rigid lower limb of de novo hemiparkinsonian patients, probably resulting from a change in their descending monoaminergic inhibitory control.
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PMID:Transmission of group II heteronymous pathways is enhanced in rigid lower limb of de novo patients with Parkinson's disease. 1218 57

In the striatum, dopamine D(2) receptors are co-localized with adenosine A(2A) receptors on the GABAergic neurons of the striopallidal pathway. Moreover, blockade of A(2A) receptors has been previously shown to suppress parkinsonian-like symptoms (catalepsy, akinesia, muscle rigidity) in rodent and primate models of Parkinson's disease (PD). Since it is believed that main motor symptoms of PD are due to the overactivity of the GABAergic striopallidal pathway, the aim of the present study was to find out whether SCH 58261, a selective antagonist of the adenosine A(2A) receptors, is capable of counteracting both the catalepsy and the enhancement of proenkephalin (PENK) mRNA expression in the rat striatum, induced by haloperidol administered at 1.5 mg/kg s.c. 3 times, every 3 h. Systemic administration of SCH 58261 (5 mg/kg i.p., 3 times, every 3 h, 10 min before haloperidol), partially decreased the haloperidol-induced catalepsy and the increase in the PENK mRNA expression in both dorsolateral and ventrolateral parts of the striatum at all three examined levels. No such changes were seen in the medial striatum and in the nucleus accumbens. Moreover, SCH 58261 given alone did not influence the level of PENK mRNA in any examined part of the striatum. The present results suggest that similarly to other A(2A) receptor antagonists, SCH 58261 normalizes activity of the striopallidal pathway, enhanced by blockade of dopamine D(2) receptors with haloperidol, which may result in recovery of motor functions.
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PMID:SCH 58261, a selective adenosine A2A receptor antagonist, decreases the haloperidol-enhanced proenkephalin mRNA expression in the rat striatum. 1283 87

The efficacy of the majority of drugs currently used for treatment of Parkinson's disease is insufficient. Moreover, such therapeutics are not devoid of serious side effects. Multiple studies on animal models of parkinsonism have shown that new class of drugs, acting selectively on metabotropic glutamate receptors (mGluRs) might be very promising for the future therapy of Parkinson's disease. This review briefly describes changes in glutamatergic transmission in the neuronal circuitry of the extrapyramidal system that occur in parkinsonian patients, contains background information on structure, function and distribution of mGluRs throughout the basal ganglia and concentrates on discussion of the results obtained from numerous animal model studies aimed to establish potential antiparkinsonian properties of various mGluR ligands. The reviewed literature data indicate that among these compounds group I mGluR antagonists and group II mGluR agonists might be beneficial to the treatment of parkinsonian akinesia and muscle rigidity.
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PMID:Role of metabotropic glutamate receptors in animal models of Parkinson's disease. 1473 87


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