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American Journal of Medical Genetics.... Jun 2011Examples of white matter hyperintensities (wmh) on magnetic resonance images in a basis pontis are presented in two male carriers, each of whom carry a small CGG...
Examples of white matter hyperintensities (wmh) on magnetic resonance images in a basis pontis are presented in two male carriers, each of whom carry a small CGG expansion fragile X mental retardation (FMR1) allele. One carried a premutation (PM) allele of 85 CGG repeats and the other, a gray zone (GZ) allele of 47 repeats. Both were originally diagnosed with idiopathic Parkinson's disease (iPD). Similar changes are also shown in one PM carrier of 99 repeats affected with mild tremor and imbalance, who was ascertained through a fragile X syndrome family. These examples draw attention to the occurrence of wmh in a basis pontis in the carriers of small CGG expansions presenting with tremor and ataxia. Moreover, the presence of this change in GZ, as well as PM, allele carriers originally diagnosed with iPD supports our earlier suggestion that both these alleles may contribute to the neurodegenerative changes in this disorder which, in the examples presented, have been reflected by wmh, most prominent in the cerebellar peduncles and/or pontine area.
Topics: Adolescent; Alleles; Case-Control Studies; Child; Child, Preschool; Female; Fragile X Mental Retardation Protein; Heterozygote; Humans; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Parkinsonian Disorders; Trinucleotide Repeat Expansion; Young Adult
PubMed: 21445959
DOI: 10.1002/ajmg.b.31189 -
Journal of Neuropathology and... Mar 2009A pathologic hallmark of Huntington disease (HD) is the presence of intraneuronal aggregates of polyglutamine-containing huntingtin protein fragments. Monoclonal...
A pathologic hallmark of Huntington disease (HD) is the presence of intraneuronal aggregates of polyglutamine-containing huntingtin protein fragments. Monoclonal antibody 1C2 is a commercial antibody to normal human TATA-binding protein that detects long stretches of glutamine residues. Using 1C2 as a surrogate marker formutant huntingtin protein, we immunostained 19 HD cases, 10 normal controls, and 10 cases of frontotemporal degeneration with ubiquitinated inclusions as diseased controls. In the HD cases, there was consistent 1C2 immunoreactivity in the neocortex, striatum, hippocampus, lateral geniculate body, basis pontis, medullary reticular formation, and cerebellar dentate nucleus. The normal and diseased controls demonstrated 1C2 immunoreactivity only in the substantia nigra, locus coeruleus, and pituitary gland. Staining of 5 HD cases and 5 normal controls revealed a less consistent and less diagnostically useful morphologic immunoreactivity profile. These results indicate that widespread 1C2 immunoreactivity is present in diverse central nervous system areas in HD, and that in the appropriate setting, 1C2 staining can be a useful tool in the postmortem diagnosis of HD when neuromelanin-containing neuronal populations are avoided.
Topics: Adult; Aged; Antibodies, Monoclonal; Brain; Child; Female; Humans; Huntington Disease; Male; Middle Aged; Peptides
PubMed: 19225411
DOI: 10.1097/NEN.0b013e318198d320 -
European Neurology 2009In 1949, Victor and Adams observed an alcoholic patient who developed quadriplegia and pseudobulbar palsy, and inability to chew, talk or swallow. A post-mortem...
In 1949, Victor and Adams observed an alcoholic patient who developed quadriplegia and pseudobulbar palsy, and inability to chew, talk or swallow. A post-mortem confirmed their suspicion of 'a large, symmetrical, essentially demyelinative lesion occupying the greater part of the basis pontis.' This paper follows the historical evolution of central pontine myelinolysis and the changing concepts of its metabolic aetiology. Too rapid a rate of correction of hyponatraemia is the most common, but not invariable aetiology.
Topics: History, 20th Century; Humans; Hyponatremia; Myelinolysis, Central Pontine
PubMed: 19033724
DOI: 10.1159/000175124 -
Acta Neuropathologica Dec 2007Neuroimaging studies indicate reduced volumes of certain gray matter regions in survivors of prematurity with periventricular leukomalacia (PVL). We hypothesized that...
Neuroimaging studies indicate reduced volumes of certain gray matter regions in survivors of prematurity with periventricular leukomalacia (PVL). We hypothesized that subacute and/or chronic gray matter lesions are increased in incidence and severity in PVL cases compared to non-PVL cases at autopsy. Forty-one cases of premature infants were divided based on cerebral white matter histology: PVL (n = 17) with cerebral white matter gliosis and focal periventricular necrosis; diffuse white matter gliosis (DWMG) (n = 17) without necrosis; and "Negative" group (n = 7) with no abnormalities. Neuronal loss was found almost exclusively in PVL, with significantly increased incidence and severity in the thalamus (38%), globus pallidus (33%), and cerebellar dentate nucleus (29%) compared to DWMG cases. The incidence of gliosis was significantly increased in PVL compared to DWMG cases in the deep gray nuclei (thalamus/basal ganglia; 50-60% of PVL cases), and basis pontis (100% of PVL cases). Thalamic and basal ganglionic lesions occur almost exclusively in infants with PVL. Gray matter lesions occur in a third or more of PVL cases suggesting that white matter injury generally does not occur in isolation, and that the term "perinatal panencephalopathy" may better describe the scope of the neuropathology.
Topics: Brain; Brain Damage, Chronic; Cerebellar Nuclei; Comorbidity; Female; Gliosis; Globus Pallidus; Humans; Infant; Infant, Newborn; Leukomalacia, Periventricular; Male; Nerve Degeneration; Nerve Fibers, Myelinated; Neurons; Premature Birth; Prevalence; Thalamus
PubMed: 17912538
DOI: 10.1007/s00401-007-0295-5 -
AJNR. American Journal of Neuroradiology Mar 2007Morphometry and spectroscopy were performed in 3 patients with fragile X-associated tremor/ataxia syndrome (FXTAS). The brain stem and cerebellum were atrophic and...
Morphometry and spectroscopy were performed in 3 patients with fragile X-associated tremor/ataxia syndrome (FXTAS). The brain stem and cerebellum were atrophic and satisfied criteria for olivopontocerebellar atrophy in 2 patients. However, the vermis was relatively spared and the basis pontis maintained its oval shape. The only spectroscopic abnormality was a decrease of the pontine N-acetylaspartate/creatine ratio in 1 patient. Atrophy and metabolic changes in FXTAS differ to some extent from those of olivopontocerebellar atrophy.
Topics: Aged; Ataxia; Brain Stem; Cerebellum; Diagnosis, Differential; Fragile X Syndrome; Humans; Magnetic Resonance Spectroscopy; Male; Protons; Tremor
PubMed: 17353317
DOI: No ID Found -
Proceedings of the National Academy of... Jan 2006The posterior cingulate and the medial parietal cortices constitute an ensemble known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29, 30, 31,...
The posterior cingulate and the medial parietal cortices constitute an ensemble known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29, 30, 31, and 7m. To understand the neural relationship of the PMC with the rest of the brain, we injected its component areas with four different anterograde and retrograde tracers in the cynomolgus monkey and found that all PMC areas are interconnected with each other and with the anterior cingulate, the mid-dorsolateral prefrontal, the lateral parietal cortices, and area TPO, as well as the thalamus, where projections from some of the PMC areas traverse in an uninterrupted bar-like manner, the dorsum of this structure from the posteriormost nuclei to its rostralmost tip. All PMC regions also receive projections from the claustrum and the basal forebrain and project to the caudate, the basis pontis, and the zona incerta. Moreover, the posterior cingulate areas are interconnected with the parahippocampal regions, whereas the medial parietal cortex projects only sparsely to the presubiculum. Although local interconnections and shared remote connections of all PMC components suggest a functional relationship among them, the distinct connections of each area with different neural structures suggests that distinct functional modules may be operating within the PMC. Our study provides a large-scale map of the PMC connections with the rest of the brain, which may serve as a useful tool for future studies of this cortical region and may contribute to elucidating its intriguing pattern of activity seen in recent functional imaging studies.
Topics: Animals; Brain; Brain Mapping; Gyrus Cinguli; Macaca; Models, Biological; Neural Pathways; Neurons; Parietal Lobe; Radionuclide Imaging; Synaptic Transmission; Thalamus; Time Factors
PubMed: 16432221
DOI: 10.1073/pnas.0507729103 -
Journal of Neurophysiology Feb 2006The paramedian pontine reticular formation contains the premotoneuronal cell groups that constitute the saccadic burst generator and control saccadic eye movements....
The paramedian pontine reticular formation contains the premotoneuronal cell groups that constitute the saccadic burst generator and control saccadic eye movements. Despite years of study and numerous investigations, the rostral portion of this area has received comparatively little attention, particularly the cell type known as long-lead burst neurons (LLBNs). Several hypotheses about the functional role of LLBNs in saccade generation have been proposed, although there is little information with which to assess them. To address this issue, I mapped and recorded LLBNs in the rostral pons to measure their discharge characteristics and correlate those characteristics with the metrics of the concurrent saccades. On the basis of their discharge and location, I identified three types of LLBNs in the rostral pons: excitatory (eLLBN), dorsal (dLLBN), and nucleus reticularis tegmenti pontis (nrtp) LLBNs. The eLLBNs, encountered throughout the pons, discharge for ipsilateral saccades in proportion to saccade amplitude, velocity, and duration. The dLLBNs, found at the pontomesencephalic junction, discharge maximally for ipsilateral saccades of a particular amplitude, usually <10 degrees , and are not associated with a particular anatomical nucleus. The nrtp LLBNs, previously described as vector LLBNs, discharge for saccades of a particular direction and sometimes a particular amplitude. The discharge of the eLLBNs suggests they drive motor neurons. The anatomical projections of the nrtp LLBNs suggest that their involvement in saccade production is less direct. The discharge of dLLBNs is consistent with a role in providing the "trigger" signal that initiates saccades.
Topics: Action Potentials; Adaptation, Physiological; Animals; Biological Clocks; Macaca mulatta; Male; Neural Inhibition; Neurons; Pons; Saccades; Time Factors; Visual Pathways
PubMed: 16236783
DOI: 10.1152/jn.00760.2005 -
Neuroscience 1999Recent electrophysiological observations suggest that, in addition to the medial septal area pacemaker system, several alternative or additional mechanisms are involved...
Recent electrophysiological observations suggest that, in addition to the medial septal area pacemaker system, several alternative or additional mechanisms are involved in the generation/regulation of hippocampal theta activity. Discharging neurons phase-locked to hippocampal theta waves have been observed in the dorsal raphe, nucleus reticularis pontis oralis and especially in the supramammillary region of rats. Since these areas are reciprocally interconnected with the hippocampal formation, including the entorhinal cortex, it would aid our understanding of limbic function to elucidate the location and neurochemical content of the entorhino-septal and septo-supramammillary projection neurons, as well as that of their postsynaptic targets. Light and electron microscopic immunostaining for calretinin, in combination with antero- and retrograde tracer techniques, postembedding immunostaining for GABA and the transmitter specific [3H]D-aspartate retrograde radiolabeling, as well as a co-localization experiment for calretinin and glutamate decarboxylase in rat supramammillary and septal neurons, demonstrated that: (i) a large population of entorhinal cells that forms asymmetric synaptic contacts on calretinin-containing neurons located at the border between the medial and lateral septal areas contains calretinin and are aspartate/glutamatergic; (ii) the overwhelming majority of calretinin-immunoreactive cells located at the border between the lateral and medial septal area are GABAergic; (iii) these neurons can be retrogradely labeled from the supramammillary area; (iv) anterogradely labeled axons originating in the border between the medial and lateral septum are GABAergic and (v) terminate on supramammillary area non-GABAergic, calretinin-containing neurons, which are known to project to the septal complex and hippocampus. These observations indicate that a large population of cells participating in the hippocampal feedback regulation of theta regulation/generation contain the same calcium-binding protein. Furthermore, entorhinal excitatory transmitter-containing neurons can depress the activity of supramammillary theta generating/regulating cells via septal inhibitory neurons.
Topics: Animals; Aspartic Acid; Axonal Transport; Calbindin 2; Entorhinal Cortex; Feedback; Female; Hippocampus; Male; Mammillary Bodies; Nerve Tissue Proteins; Neural Pathways; Neurons; Phytohemagglutinins; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein G; Septal Nuclei; Theta Rhythm; gamma-Aminobutyric Acid
PubMed: 10363811
DOI: 10.1016/s0306-4522(98)00245-0 -
The Journal of Biological Chemistry Mar 1999Three separate classes of ribonucleotide reductases are known, each with a distinct protein structure. One common feature of all enzymes is that a single protein...
Three separate classes of ribonucleotide reductases are known, each with a distinct protein structure. One common feature of all enzymes is that a single protein generates each of the four deoxyribonucleotides. Class I and III enzymes contain an allosteric substrate specificity site capable of binding effectors (ATP or various deoxyribonucleoside triphosphates) that direct enzyme specificity. Some (but not all) enzymes contain a second allosteric site that binds only ATP or dATP. Binding of dATP to this site inhibits the activity of these enzymes. X-ray crystallography has localized the two sites within the structure of the Escherichia coli class I enzyme and identified effector-binding amino acids. Here, we have studied the regulation of three class II enzymes, one from the archaebacterium Thermoplasma acidophilum and two from eubacteria (Lactobacillus leichmannii and Thermotoga maritima). Each enzyme has an allosteric site that binds ATP or various deoxyribonucleoside triphosphates and that regulates its substrate specificity according to the same rules as for class I and III enzymes. dATP does not inhibit enzyme activity, suggesting the absence of a second active allosteric site. For the L. leichmannii and T. maritima enzymes, binding experiments also indicate the presence of only one allosteric site. Their primary sequences suggest that these enzymes lack the structural requirements for a second site. In contrast, the T. acidophilum enzyme binds dATP at two separate sites, and its sequence contains putative effector-binding amino acids for a second site. The presence of a second site without apparent physiological function leads to the hypothesis that a functional site was present early during the evolution of ribonucleotide reductases, but that its function was lost from the T. acidophilum enzyme. The other two B12 enzymes lost not only the function, but also the structural basis for the site. Also a large subgroup (Ib) of class I enzymes, but none of the investigated class III enzymes, has lost this site. This is further indirect evidence that class II and I enzymes may have arisen by divergent evolution from class III enzymes.
Topics: Allosteric Regulation; Amino Acid Sequence; Biopolymers; Lactobacillus; Molecular Sequence Data; Oxidation-Reduction; Protein Binding; Ribonucleotide Reductases; Ribonucleotides; Sequence Homology, Amino Acid; Thermoplasma; Thermotoga maritima; Vitamin B 12
PubMed: 10066778
DOI: 10.1074/jbc.274.11.7182 -
Nihon Ronen Igakkai Zasshi. Japanese... Mar 1998We reviewed MRI findings in a series of 211 patients with cerebral infarction. A high signal in the basis pontis bilaterally in T2 weighted images (Central Pontine...
We reviewed MRI findings in a series of 211 patients with cerebral infarction. A high signal in the basis pontis bilaterally in T2 weighted images (Central Pontine Hyperintensity, CPH), with almost-normal T1 weighted images, was present in 29 cases (12.9%). CPH findings were present more frequently in elderly patients, and were significantly associated with a previous history of cerebrovascular accident, although not with other arteriosclerotic risk factors. In patients with CPH. periventricular hyperintensity was severe and the number of infarctions of the thalamus was higher. These results suggest that a) CPH may arise from ischemia in subcortical areas or in the territory of the vertebrobasilar system, and that b) chronic brain ischemia, which may be partially due to aging, may play a more important role in cerebral infarction than the usual arteriosclerotic risk factors.
Topics: Adult; Aged; Aged, 80 and over; Cerebral Infarction; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pons
PubMed: 9597880
DOI: 10.3143/geriatrics.35.208