Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been slightly over 100 years since Sir James Paget's classic descriptions of "osteitis deformans" first appeared. He had described the mid- to late stages of patients with the chronic, debilitating, rare, and polyostotic forms of the disease. It is now known that the milder forms of the disease are quite common particularly in those of Anglo-Saxon ancestry. He believed the condition to be a chronic inflammation of unknown etiology because of its asymmetrical skeletal distribution, chronicity, and the gross appearance of the bones. With regard to the possible etiology of Paget's disease of bone, nothing worthy of note had been discovered until 1974 when viral-like inclusions were reported within the osteoclasts of all Paget's disease patients. In the ensuing decade, a great deal more circumstantial evidence from electron microscopic and immunologic studies supports the view that Paget's disease represents a slow virus infection. This article deals with the possible to probable viral etiology of Paget's disease with respect to its pathogenesis and its potential for eventual eradication. For many years Paget's disease was considered a disease almost exclusively confined to adulthood. Evidence now suggests that "familial chronic hyperphosphatasemia" represents the childhood form of Paget's disease.
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PMID:Pathogenesis of Paget's disease based on viral etiology. 354 89

A 60-year-old woman with superficial spreading melanoma in situ, measuring 2.5 mm in diameter, was examined. She had noticed a very small pigmented lesion 1.2 mm in diameter on her left lower leg in April of 1989. By April of 1990, it had grown to 2.5 mm in diameter. Its edge was irregular, and its color was variegated black to brown. Skin surface markings had disappeared in the center portion. Histopathologically, the lesion was asymmetrical. Atypical large cells nested in the lower epidermis and were scattered singly in the mid and upper epidermis, as seen in Paget's disease. At the periphery of the lesion, single large tumor cells were scattered in the mid epidermis. The tumor cells reacted to monoclonal anti-melanoma antibody HMB-45.
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PMID:A case of superficial spreading melanoma in situ 2.5 mm in diameter. 840 26

Bipedal locomotion and fine motility of hand and larynx of humans introduced musculoskeletal adaptations, new pyramidal, corticostriatal, corticobulbar, nigrostriatal, and cerebellar pathways and expansions of prefrontal, cingular, parieto-temporal and occipital cortices with derived new brain capabilities. All selectively degenerate in aged homo sapiens following 16 syndromic presentations: (1) Parkinsonism: nigrostriatal control for fast automatic movements of hand, larynx, bipedal posture and gait ("simian gait and hand"). (2) Frontal (highest level) gait disorders (lower body parkinsonism, gait apraxia, retropulsion): prefrontostriatal executive control of bipedal locomotion. (3) ataxia: new synergistic coordination of bipedal gait and fine motility. (4) Dyskinesias (chorea, dystonia, tremor...): intrusions of simian basal ganglia motor subroutines. (5) motoneuron diseases: new proximo-distal and bulbar motoneurones, preserving older ones (oculomotor, abdominal...). (6) Archaic reflexes: prefrontal disinhibition of old mother/tree-climbing-oriented reflexes (sucking, grasping, Babinski/triple retraction, gegenhalten), group alarms (laughter, crying, yawning, grunting...) or grooming (tremor=scratching). (7) Dysautonomia: contextual regulation (orthostatism...). (8) REM sleep disorders of new cortical functions. (9) Corticobasal syndrome: melokinetic control of hand prehension-manipulation and language (retrocession to simian patterns). (10) Frontal/temporal lobe degeneration: medial-orbitofrontal behavioural variant: self monitoring of internal needs and social context: apathy, loss of personal hygiene, stereotypia, disinhibition, loss of concern for consequences of acts, social rules, danger and empathy; dorsolateral executive variant: inadequacy to the context of action (goal, environmental changes...); progressive non-fluent aphasia: executive and praxic processing of speech; temporal variant: abstract concepts for speech, gestures and vision (semantic dementia, progressive nonfluent aphasia) (11) Temporomesial-limbic-paralimbic-associative cortical dementias (Alzheimer's disease, Lewy body, progressive amnesia): processing of explicit cognition: amnesic syndrome, processing of hand, larynx and eye: disorientation, ideomotor apraxia, agnosia, visuospatial processing, transcortical aphasia. (12) Focal posterior atrophy (Benson, progressive apraxia): visuomotor processing of what and where. (13) Macular degeneration: retinal "spot" for explicit symbols. (14) "Psychiatric syndromes": metacognition, self monitoring and regulation of hierarchical processing of metacognition: hallucinations, delusions, magic and mystic logic, delusions, confabulations; drive: impulsivity, obsessive-compulsive disorders, mental automatisms; social interactions: theory of mind, autism, Asperger. (15) Mood disorders: control on emotions: anxio-depressive and bipolar disorders, moria, emotional lability. (16) Musculoskeletal: inclusion body myositis: muscles for bipedal gait and fine motility. Paget's disease: bones for bipedal gait and cranium. Understanding of the genetic mechanisms underlying the evolution of these recent human brain regions and paleoneurology my be the key to the focal, asymmetrical or systemic character of neurodegeneration, the pathologic heterogeneity/overlap of syndromic presentations associating gait, hand, language, cognition, mood and behaviour disorders.
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PMID:Paleoneurology: neurodegenerative diseases are age-related diseases of specific brain regions recently developed by Homo sapiens. 1870 90

The complete three-dimensional sensory module structures of the Pr ground state of Synechocystis 6803 Cph1 and the unusual Pfr ground state of the bacteriophytochrome PaBphP (PDB codes 2VEA and 3C2W respectively) have now been solved, revealing an asymmetrical dumbbell form made up of a PAS (Period/ARNT/Singleminded)-GAF (cGMP phosphodiesterase/adenylate cyclase/FhlA) bidomain carrying the chromophore and the smaller PHY (phytochrome-specific) domain. The PHY domain is structurally related to the GAF family, but carries an unusual tongue-like structure which contacts the larger lobe to seal the chromophore pocket. In 2VEA, the tongue makes intimate contact with the helical N-terminus; both the N-terminus and the tongue structures are quite different in 3C2W. As expected, the structures reveal ZZZssa and ZZEssa chromophore conformations in 2VEA and 3C2W respectively, associated with tautomeric differences in several nearby tyrosine residues. Two salt bridges on opposite sides of the chromophore, as well as the associations of the C-ring propionates also differ. It is still unclear, however, which of these structural differences are associated with bacteriophytochromes compared with Cph1 and plant-type phytochromes, the unusual 3C2W Pfr ground state functionality compared with the Pr ground state or the Pr compared with Pfr photoisomerism. To access the latter unambiguously, both Pr and Pfr structures of the same molecule are required. New solid-phase NMR data for Cph1 in the Pr, Pfr and freeze-trapped intermediate states reveal unexpected changes in the chromophore during Pfr-->Pr photoconversion. These, together with our efforts to solve the three-dimensional structure of a complete phytochrome molecule are also described.
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PMID:Phytochrome three-dimensional structures and functions. 2029 48

Craniovertebral dislocation is uncommon, but its diagnosis is important taking into account the potential severity of the neurologic complications. A number of causes are known; the most common are Down syndrome, rheumatoid arthritis, Paget's disease, other metabolic bone diseases, and craniocervical trauma. Down's syndrome is a relatively common clinical condition but craniovertebral subluxation is only observed in a small percentage of patients. About half of all cervical spine injuries affect the atlanto-occipital region and C2 vertebra. In rheumatoid arthritis, craniocervical dislocation occurs in up to 40% of patients with severe disease. In Paget's disease, involvement of the craniovertebral region occurs in about 30% of all cases. The clinical neurologic syndrome is characterized by local pain, features of upper spinal cord and medullary compression, positive Lhermitte phenomenon, syncope associated with neck flexion, vertebral artery obstruction or dissection leading to stroke, and asymmetrical lower cranial nerve palsies. Neuroimaging is essential to confirm the clinical diagnosis and to categorize severity. The treatment of this disorder is usually surgical, but traction and external immobilization is relevant in some cases. Specific conditions may require additional treatments such as radiotherapy, antibiotics, or chemotherapy.
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PMID:Neurologic complications of craniovertebral dislocation. 2436 11

Paget's disease of bone (PDB) is a localized, chronic bone metabolic disorder, characterized by an osteoclastic malfunction, causing increased bone resorption and subsequent compensatory creation of new bone with a defective microstructure. Monostotic cases of PDB are less common than asymmetrical polyostotic PDB cases. The radiological diagnosis of PDB is usually straightforward, but monostotic cases can cause diagnostic difficulties. We report a case of monostotic PDB in a 64-year-old man. He experienced pain of the left lower extremity and radiological investigations revealed irregular areas of bone destruction in the left femur. Bone biopsy findings indicated PDB. Treatment with bisphosphonates was initiated, but after about three years of treatment left hip arthroplasty was required due to a large area of bone destruction. Presentation of this case report aims to discuss diagnostic challenges of monostotic cases of PDB and present guidelines of treatment.
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PMID:Monostotic Paget's disease of bone - literature review and case report. 3146 33