Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are many theories concerning the etiology of chondromalacia patellae, as well as many points which have not been fully investigated yet. Using rabbits experimentally, shortening and elongation of the 3 mm patellar ligament were performed, producing the changes of contact surface and pressure on the patellar cartilage, and the patellar cartilage and the subchondral bone were studied sequentially. In the group of shortening, after the course of 16 weeks, no particular changes were recognized in the cartilage and the subchondral bone, compared with the control. In the group with elongation, 2-4 weeks after the operation, thinning of the trabecular and the subchondral bone, proliferation of blood vessels in the subchondral bone and their invasion into the calcified cartilage, were seen, without abnormality in the articular cartilage. After 4 weeks, irregularity or disappearance of the tide mark and degeneration of the ground substance toward the deep layer of the cartilage began to be recognized. After 8 weeks fasciculation was produced in the ground substance from the deep to the middle layers of the cartilage. After 12 weeks, degeneration extended to the superficial layer of the cartilage, producing blister formation, fibrillation and fissura, and finally proceeding to the desquamation of the superficial layer, degeneration and decrease in the thickness of the cartilage. These findings are similar to the histological findings of chondromalacia patellae, and seem to be different from those of arthrosis deformans in the bony changes. It is further suggested that decrease of contact surface and pressure on the cartilage can be considered to be one of the causes for chondromalacia patellae.
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PMID:[Experimental study of chondromalacia patellae (author's transl)]. 733 51

The corpus callosum results from neocortical commissural axon fasciculation. Its development reflects the interhemispheric circuitry and then follows the successive steps of synaptogenesis. The first stage consists of callosal neuron differentiation, which allows the extention of the future callosal axon; this is an early event that occurs while neuronal migration to the cortical plate is still ongoing. Callosal axon guidance towards its specific target is the second step which includes reaching and crossing the midline and further target recognition with formation of initial synapses. This period extends from 12 to 22 post-conceptional weeks and corresponds to the following histological features: i) progressive invasion by callosal growth cones of the dorsal part of lamina reuniens through a preformed glial pathway; ii) appearence of the three parts of corpus callosum, namely truncus, rostrum and lastly the splenium. Both these stages are genetically controlled either directly by developmental gene expression (neurogenesis genes) or indirectly by the establishment of cue maps (spatial expression of extra-cellular matrix proteins). The third step is that of synapse remodeling by synaptic activity, giving rise to axonal elimination, macroscopically revealed by a transitory thinning of corpus callosum. This perinatal event contributes to the corpus callosum acquiring a mature topography. Finally, analysis of corpus callosum ontogenesis appears as a striking model of synaptogenesis study and provides physiopathological assumptions for a understanding of the corpus callosum agenesis.
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PMID:[Histogenesis of the corpus callosum]. 975 25

Neural cell adhesion molecules (CAM) play important roles in neural development, neurite outgrowth, axonal guidance, fasciculation and synapse formation. Neuropathological studies of X-linked hydrocephalus (XLH) associated with L1 CAM mutations emphasize marked hypoplasia of the pyramidal tract, agenesis of the corpus callosum and septum pellucidum, and a thin cerebral mantle with hypoplastic white matter, but there are no detailed studies of the cerebral cortex in the literature. We report clinical, neuroimaging, and neuropathological findings in three boys with XLH. All had severe congenital hydrocephalus with marked thinning of the cerebral mantle and severe development disabilities. The brain specimens from the three boys showed both pachygyria and polymicrogyria, hypoplasia of the medullary pyramids, hypoplasia of the corpus callosum, small anterior commissure, hypoplasia and poorly differentiated hippocampi. A small but patent aqueduct was present in all three brains. Despite the extensive cerebral malformations, the cortex in all three brains showed normal-appearing laminar cortical neuronal architecture and absence of gliosis. In XLH, it is likely that the poor developmental outcome of spasticity, contractures and severe mental retardation results from a disturbance of neuronal connectivity, fasciculation, and synapse formation rather than aqueductal stenosis, increased intracranial pressure, or abnormal neuroblast migration.
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PMID:The pachygyria-polymicrogyria spectrum of cortical dysplasia in X-linked hydrocephalus. 992 16

There has been several reports of an MND like syndrome in HIV-1 infection, however the data is still sparse. Furthermore, HIV-associated amyotrophic lateral sclerosis (ALS) syndrome differs from the classical ALS in some key aspects.. A 44-year-old male presented with a history of insidious onset and gradually progressive asymmetric weakness of lower limbs. He also complained of thinning in both legs, the left leg more than the right since 1 year along with spontaneous twitching of muscles in both the thighs. On neurological examination, the assessment of higher mental functions was normal. There were no cranial nerve deficits. Motor power was grade 5/5 (Medical Research Council scale) in both the upper limbs and 4+ at hips and knees bilaterally, 5 at right ankle, and 4+ at left ankle. All the deep tendon reflexes were brisk with extensor planter responses. There were no cerebellar signs or sensory deficits. HIV-1 was reactive in enzyme-linked immunosorbent assay. Electrophysiological studies were conducted per the MND protocol.None of the nerves studied showed an abnormal drop in compound muscle action potential amplitude with proximal stimulation. There was evidence of diffuse spontaneous activity, which manifests as fibrillation and fasciculation potentials in most muscles tested . Overall there seems to be sufficient evidence to implicate HIV as a potential cause of an ALS-like disorder, but one must also consider the possibility of coincidental HIV infection in patients who have sporadic ALS.
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PMID:Amyotrophic lateral sclerosis-like presentation in a HIV-positive patient. 2484 49

Tuberous Sclerosis Complex (TSC) is a rare genetic disease that manifests with early symptoms, including cortical malformations, childhood epilepsy, and TSC-associated neuropsychiatric disorders (TANDs). Cortical malformations arise during embryonic development and have been linked to childhood epilepsy before, but the underlying mechanisms of this relationship remain insufficiently understood. Zebrafish have emerged as a convenient model to study elementary neurodevelopment; however, without in-depth functional analysis, the Tsc2-deficient zebrafish line cannot be used for studies of TANDs or new drug screening. In this study, we found that the lack of Tsc2 in zebrafish resulted in heterotopias and hyperactivation of the mTorC1 pathway in pallial regions, which are homologous to the mammalian cortex. We observed commissural thinning that was responsible for brain dysconnectivity, recapitulating TSC pathology in human patients. The lack of Tsc2 also delayed axonal development and caused aberrant tract fasciculation, corresponding to the abnormal expression of genes involved in axon navigation. The mutants underwent epileptogenesis that resulted in nonmotor seizures and exhibited increased anxiety-like behavior. We further mapped discrete parameters of locomotor activity to epilepsy-like and anxiety-like behaviors, which were rescued by reducing tyrosine receptor kinase B (TrkB) signaling. Moreover, in contrast to treatment with vigabatrin and rapamycin, TrkB inhibition rescued brain dysconnectivity and anxiety-like behavior. These data reveal that commissural thinning results in the aberrant regulation of anxiety, providing a mechanistic link between brain anatomy and human TANDs. Our findings also implicate TrkB signaling in the complex pathology of TSC and reveal a therapeutic target.
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PMID:TrkB hyperactivity contributes to brain dysconnectivity, epileptogenesis, and anxiety in zebrafish model of Tuberous Sclerosis Complex. 3193 27