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PubMedDate not supplied

Leptomeningeal lipomatous hamartoma overlying a midline cleft of the ventral pons.

Intracranial lipomatous hamartomas (lipomas) are of maldevelopmental nature and have a predilection for the midsagittal plane. They are often associated with malformations of the CNS and other organ systems. It is reported an asymptomatic lipomatous hamartoma of the ventral pontine leptomeninges and a midline cleft of the subjacent pons discovered incidentally at autopsy of an 80-year-old man. Review of the literature shows that this type of lesion at the ventral pons has not been reported previously.

Aged↗
PubMed1995

Neuronal ceroid lipofuscinosis in the Polish Owczarek Nizinny (PON) dog. A retinal study.

Visual dysfunction and neurological symptoms were found in Polish Owczarek Nizinny (PON) dogs. Two dogs were examined, one at 2 years of age and the other one at 4 years. The oldest dog was totally blind. The 2-year-old dog developed mental disturbances and the 4-year-old dog became severely ataxic. Ophthalmoscopical findings were retinal hyper-reflectivity, attenuation of the retinal vessels and the presence of greyish to brown spots in the fundus. Electrophysiological and ultrastructural studies were performed in the 2-year-old dog. Scotopic ERG responses were absent, whereas 30 Hz cone flicker responses were recordable, although with an amplitude reduced to about 30% of the normal level. A slow negative potential replaced the c-wave, indicating a dysfunction of the RPE. Intracellular inclusions with a granular appearance or containing membranous fingerprint-like or curvilinear profiles, resembling ceroid, were found in different retinal cells. The RPE cells in the central areas were charged with autofluorescent material having similar structure, Photoreceptor degeneration was most severe in the central areas, corresponding to the RPE changes. It appears than the PON dog may provide a new animal model for neuronal ceroid lipofuscinosis.

Animals↗
PubMedDate not supplied

Co-localization of neuropeptide tyrosine (NPY) and its C-terminal flanking peptide (C-PON).

Neuropeptide tyrosine (NPY) is one of the most abundant and widespread peptides in the mammalian nervous system. Recent isolation and sequencing of the DNA encoding NPY has predicted the existence of a 97 amino acid precursor peptide. Proteolytic processing of this precursor could yield three separate peptide products, an N-terminal signal peptide, neuropeptide tyrosine and a 30 amino acid C-terminal flanking peptide (C-PON). Here, we present evidence that the predicted C-flanking peptide of NPY is widely distributed in both the central and peripheral nervous systems of several mammalian species including man, and has an identical distribution to NPY. It was also demonstrated, using correlative light microscopic immunostaining on serial sections and double electron microscopic immunocytochemistry, that C-PON and NPY immunoreactivities are co-localized in neuronal cell bodies of the brain cortex, sympathetic ganglion cells, norepinephrine-containing granules of the adrenal medulla and in human pheochromocytoma tumor cells.

Adrenal Gland Neoplasms↗
PubMed2001

Apolipoprotein A-I promotes the formation of phosphatidylcholine core aldehydes that are hydrolyzed by paraoxonase (PON-1) during high density lipoprotein oxidation with a peroxynitrite donor.

High density lipoprotein (HDL) is rich in polyunsaturated phospholipids that are sensitive to oxidation. However, the effect of apolipoprotein A-I and paraoxonase-1 (PON-1) on phosphatidylcholine oxidation products has not been identified. We subjected native HDL, trypsinized HDL, and HDL lipid suspensions to oxidation by the peroxynitrite donor, 3-morpholinosydnonimine. HDL had a basal level of phosphatidylcholine mono- and di-hydroperoxides that increased to a greater extent in HDL, compared with either trypsinized HDL or HDL lipid alone. Phosphatidylcholine core aldehydes, which were present in small amounts, increased 10-fold during oxidation of native HDL, compared with trypsinized HDL (p = 0.004), and 4-fold compared with HDL lipid suspensions (p = 0.0021). In addition, the content of lysophosphatidylcholine increased 300% during oxidation of native HDL, but only 80 and 25%, respectively, during oxidation of trypsinized HDL and HDL lipid suspensions. Phosphatidylcholine isoprostanes accumulated in comparable amounts during the oxidation of all three preparations. Incubation of apolipoprotein A-I with 1-palmitoyl-2-linoleoyl glycerophosphocholine proteoliposomes in the presence of 3-morpholinosydnonimine or apoAI with phosphatidylcholine hydroperoxides resulted in a significant increase in phosphatidylcholine core aldehydes with no formation of lysophosphatidylcholine. We propose that apolipoprotein A-I catalyzes a one-electron oxidation of alkoxyl radicals. Purified PON-1 hydrolyzed phosphatidylcholine core aldehydes to lysophosphatidylcholine. We conclude that, upon HDL oxidation with peroxynitrite, apolipoprotein AI increases the formation of phosphatidylcholine core aldehydes that are subsequently hydrolyzed by PON1.

Aldehydes↗
PubMed1994

Multiple sclerosis lesions of the auditory pons are not silent.

To understand the relationship between brainstem lesions and auditory neurology in patients with multiple sclerosis, we compared behavioural, electrophysiological and imaging data in 38 patients with probable or definite multiple sclerosis and normal or near normal hearing. Behavioural measures included (i) general hearing tests (audiogram, speech discrimination) and (ii) hearing tests likely to be critically dependent upon brainstem processing (masking level difference, interaural time and level discrimination). Brainstem auditory evoked potentials provided the electrophysiological data. Multiplanar high-resolution MRI of the brainstem provided the anatomical data. Interaural time discrimination for high-frequency sounds was by far the most sensitive of all tests with abnormalities in 71% of all subjects. Whenever any other test was abnormal this test was always abnormal. Interaural time discrimination for low-frequency sounds and evoked potentials were closely related and next most sensitive with abnormalities in approximately 40% of all subjects. Interaural level discrimination and masking level difference were least sensitive with abnormalities in < 10% of subjects. Speech discrimination scores correlated significantly with the masking level differences, as well as with interaural time discrimination for high-frequency sounds. Pontine lesions were found in five of the 16 patients, in whom an objective method for detecting magnetic resonance lesions could be applied. All four with lesions involving the pontine auditory pathway had marked abnormalities in interaural time discrimination and evoked potentials. None of the other 12 had evoked potentials abnormalities. We conclude that neurological tests requiring precise neural timing can reveal behavioural deficits for multiple sclerosis lesions of the auditory pons that are otherwise 'silent'. Of all neurological systems the auditory system at the level of the pons is probably the most sensitive to multiple sclerosis lesions, because of its exceptional dependence upon neural timing in the microsecond range and the lack of redundancy in the encoding of high-frequency sounds. Precise neural timing may be critical for some aspects of speech processing.

Adult↗
PubMed2005

Polymorphisms in the PON gene cluster are associated with Alzheimer disease.

Paraoxonase is an arylesterase enzyme that is expressed in the liver and found in the circulation in association with apoA1 and the high-density lipoprotein, and prevents the accumulation of oxidized lipids in low-density lipoproteins in vitro. Common polymorphisms in genes encoding paraoxonase are established risk factors in a variety of vascular disorders including coronary artery disease and carotid artery stenosis, but their association with Alzheimer disease (AD) is controversial. We tested the association of 29 SNPs in PON1, PON2 and PON3 with AD in 730 Caucasian and 467 African American participants of the MIRAGE Study, an ongoing multi-center family-based genetic epidemiology study of AD. Eight SNPs were associated with AD in the African American families (0.0001< or =P< or =0.04) and two SNPs were associated with AD in Caucasian families (0.01< or =P< or =0.04). Of note, the pattern of association for the PON1 promoter SNP -161[C/T] was the same in both ethnic groups (P=0.006). Haplotype analysis using sliding windows revealed 11 contiguous SNP combinations spanning the three PON genes with significant global test scores (0.006< or =P< or =0.04) in the two ethnic groups combined. The most significantly associated haplotype comprised SNPs in the region spanning the -161[C/T] SNP (P=0.00009). Our results demonstrate association between AD and variants in the PON gene cluster in Caucasians and African Americans.

Black or African American↗
PubMed1997

Suspected acute encephalopathy with symmetrical abnormal signal areas in the basal ganglia, thalamus, midbrain and pons diagnosed by magnetic resonance imaging.

A 4-year-old boy was admitted with disturbed consciousness following a convulsion. He developed bilateral pyramidal tract signs and showed a decerebrate posture. Laboratory findings revealed severe liver dysfunction and disseminated intravascular coagulation. On the eighth day eight in hospital he developed parkinsonism. However, 5 months from onset he had recovered almost completely. Brain CT on admission showed low density areas in the basal ganglia, thalamus, midbrain and pons. A T2-weighted scan in magnetic resonance imaging (MRI) showed almost symmetrical high signal intensities in both basal ganglia (including putamen, caudate nucleus, globus pallidus), external capsule, internal capsule thalamus, midbrain, pons and white matter of the peribasal ganglia; but a T1-weighted scan showed low signal intensities in the same regions during all phases. Therefore hemorrhagic lesions or the presence of thalamic methemoglobin were excluded. It was considered that the pathogenesis may be cytotoxic cellular edema due to cytotoxic agents or acute metabolic factors. Clinical presentation, laboratory findings and radiological findings were most suggestive of acute necrotizing encephalopathy. As differential diagnoses, acute disseminated encephalomyelitis and brainstem encephalitis were considered.

Acute Disease↗
PubMed2003

Extensive association analysis between polymorphisms of PON gene cluster with coronary heart disease in Chinese Han population.

OBJECTIVE: An extensive association analysis of PON gene cluster (PONs) with coronary heart disease (CHD) was performed in Chinese Han population. METHODS AND RESULTS: Thirty polymorphisms of PON1, PON2, and PON3 gene were identified by direct sequencing of genomic DNA derived from 48 randomly selected patients. Twelve polymorphisms were additionally investigated for association with CHD in 474 male patients and 475 controls. Univariate analyses showed the cases had significantly higher frequencies of PON1 192Q allele, 160R allele, -162A allele, and PON2 311C allele than were seen in the controls. Logistic regression analyses revealed only the PON1 R160G and -162G/A polymorphisms remained significantly associated with CHD (P=0.0054 and P=0.0002). Haplotype analyses for various polymorphism combinations additionally confirmed the results of individual polymorphism analyses. Only the frequencies of haplotypes containing -162A allele were significantly higher, whereas only the frequencies of haplotypes containing 160G allele were significantly lower in cases than in controls in various polymorphism combinations. CONCLUSIONS: This extensive association study has identified the PON1 -162G/A and R160G polymorphisms to be independently associated with CHD in Chinese Han population and warrants additional study to elucidate the biological mechanism.

Alleles↗
PubMed2002

The risk of coronary artery disease in population of Taiwan is associated with Cys-Ser 311 polymorphism of human paraoxonase (PON)-2 gene.

BACKGROUND: Paraoxonase (PON), a high density lipoprotein (HDL)-associated enzyme, is capable of inhibiting low density lipoprotein (LDL) oxidation by destroying the biologically active phospholipids in oxidatively modified LDL. An increased risk of coronary artery disease (CAD) has shown to associate with polymorphisms of PON gene (PON1) in different population. The risk of CAD associated with the other PON1-like gene, designated PON2, which has a similar function and is structurally related to PON1, is least discussed. A population-based case-control study was conducted to investigate the association between CAD and the polymorphisms at two common codons 148 and 311 of PON2 in the population of Taiwan. METHODS: Totally 364 unrelated, angiographically proved CAD-positive patients (338 male and 26 female) and 337 unrelated, CAD-free control subjects (249 male and 88 female) enrolled in this study. Lipids and lipoproteins profile and the association of PON2 genotypes and allele frequencies were analyzed in all study cohorts. RESULTS: The plasma levels of HDL-cholesterol and apoA-I were significantly lower in patients with CAD than in control subjects (both p = 0.0001). There was no difference in the genotype frequency distribution at codon 148 of PON2 between CAD patients and the controls. However, age-, sex- and diabetes-adjusted odds ratios for individuals with the SS genotype of the codon 311 polymorphism (Cys --> Ser, PON2*C allele --> PON2*S allele) showed a 4.6-fold higher risk of CAD (95% CI = 1.6-15.3, p = 0.006) they ran. Also, in the control subjects, PON2*C allele carriers (CC and CS genotypes) had higher plasma levels of HDL than cases with the SS genotypes (p = 0.035 and p = 0.012, respectively). CONCLUSIONS: Our data implicate that the genotypic variation at codon 311 of PON2 contributes to the susceptibility of CAD in the population of Taiwan.

Adult↗
PubMed2003

[A case of bilateral lower pons-medial medullary infarction presenting quadriparesis].

Bilateral medial medullary infarction is rare. Only 18 cases have been reported previously. We experienced a case of the bilateral lower pons-medullary infarction. A 63-year-old woman was admitted to our hospital because of moderate left hemiparesis. Hyperreflexia in left limbs and positive Babinski's reflex in left foot was observed. Sensory disturbance was mild left hemihypesthesia (in light touch, postural sense and vibration) without facial involvement. She also had lateral gaze nystagmus, dysarthria, and bilateral decreased gag reflex. Respiratory failure was not observed. A conservative therapy for cerebral infarction was performed. But the hemiparesis was deteriorated and progressed to complete quadriparesis on the 5th day. The brain MRI (T2-weighted image and FLAIR) demonstrated bilateral lower pons-medial medullary infarction on the 9th day. Cerebral angiography and 3D-CT angiography revealed no stenosis or occlusions in the major cerebral arteries. The anterior spinal artery was not evaluated enough because of the arteriosclerosis. The prognosis of this patient was favorable except for the quadriparesis. The severe quadriparesis has not been improved for about 2 years. The bilateral medial medullary infarction was quite rare in the literature. The prognoses of these cases were unfavorable for the respiratory failure. Our case was not fatal because of no respiratory paralysis.

Female↗
PubMed2005

[Association analysis between polymorphisms of PON gene cluster with coronary heart disease in Chinese].

An extensive association analysis of PON gene cluster (PONs) with coronary heart disease (CHD) was performed in Chinese Han population. Eleven polymorphisms of PON1, PON2 and PON3 gene were investigated for association with CHD in 474 male patients and 475 controls. Univariate analyses showed the cases had significantly higher frequencies of PON1 192Q allele, 160R allele, -162A allele and PON2 311C allele than were seen in the controls. Logistic regression analyses revealed only the PON1 R160G and -162G/A polymorphisms remained significantly associated with CHD (P = 0.0054 and P = 0.0002). Haplotype analyses for various polymorphism combinations further confirmed the results of individual polymorphism analyses. Only the frequencies of haplotypes containing -162A allele were significantly higher,whereas only the frequencies of haplotypes containing 160G allele significantly lower in cases than those in controls in various polymorphism combinations. This extensive association study has identified the PON1 -162G/A and R160G polymorphisms to be independently associated with CHD in Chinese Han population,and warrants further study to elucidate the biological mechanism.

Adult↗
PubMed1990

Neuropeptide tyrosine (NPY) and its C-terminal flanking peptide (C-PON) in the developing and adult spinal cord of a reptile.

The developmental pattern and the adult distribution of neuropeptide tyrosine (NPY) and its C-terminal flanking peptide (C-PON) were investigated in the spinal cord of the lizard Gallotia galloti. Embryonic, postnatal and adult animals were studied by means of the immunohistochemical technique. Neurons containing both peptide immunoreactivities first appeared at the embryonic Stages 37/38. Immunoreactive perikarya were more numerous in the embryonic than in either the postnatal or the adult spinal cord. Fibres immunoreactive for both antisera appeared around the time of hatching, being numerous and widespread in the adult spinal cord. NPY- and C-PON-like-containing neurons and fibres in the adult spinal cord of Gallotia galloti were related to sensory, autonomic and motor areas.

Animals↗
PubMed1980

Unilateral gunshot wound of the pons: clinical, electrophysiologic, and neuroradiologic correlates.

Following a gunshot wound to the face, a 17-year-old male patient experienced a right trigeminal and abducens paralysis, dysarthria, right-sided ataxia, left-sided weakness of the lower part of the face and limbs, and left-sided sensory loss from his neck down. Brainstem auditory evoked potentials showed a decreased P5/P1 amplitude ratio for left ear presentation, and inconsistent replication of P2 and P3 on the right and, to a lesser extent, on left ear click presentations. A computerized tomography scan showed right pontine atrophy. These findings point to a unilateral lesion of the right pons.

Adolescent↗
PubMed1989

Lacunar infarct of the tegmentum of the lower lateral pons.

A stroke with a somewhat unusual neurologic formula was correlated with a small linear high-intensity T2 focus in the lateral tegmentum of the lower third of the pons. The clinical features included dysarthria, staggering gait, incoordination of handwriting, right facial weakness, nystagmus, ocular overshoot, right appendicular ataxia, and left-sided dissociated sensory loss for pain and temperature. Lacunar lesions of the tegmentum in the region of the pontomedullary junction, while not uncommon, have not been studied pathologically and have not been reported in the magnetic resonance imaging literature, to my knowledge.

Cerebral Infarction↗
PubMed1996

Common patterns of increased and decreased fos expression in midbrain and pons evoked by noxious deep somatic and noxious visceral manipulations in the rat.

Immunohistochemical detection of the protein product (Fos) of the c-fos immediate early gene was used to study neuronal activation in the rostral pons and midbrain of halothane-anesthetised rats following noxious deep somatic or noxious visceral stimulation. In animals exposed only to halothane anesthesia, Fos-like immunoreactive (IR) neurons were located in the midbrain periaqueductal gray matter, tectum, and parabrachial nucleus. Following noxious stimulation of hindlimb muscle, knee joint, vagal cardiopulmonary, or peritoneal nociceptors, there was, compared to halothane-only animals, a significant increase in the numbers of Fos-like (IR) cells in the caudal ventrolateral periaqueductal gray and the intermediate gray lamina of the superior colliculus. Given the general agreement that increased Fos expression is a consequence of increased neuronal activity, the finding that a range of noxious deep somatic and noxious visceral stimuli evoked increased neuronal activity in a discrete, caudal ventrolateral periaqueductal gray region is consistent with previous suggestions that this region is an integrator of deep noxious evoked reactions. The noxious deep somatic and noxious visceral manipulations also evoked, compared to halothane-only animals, reductions in the numbers of Fos-like IR cells in the stratum opticum of the superior colliculus and the unlaminated portion of the external subnucleus of the inferior colliculus. To our knowledge this is the first report of reductions in Fos-expression in the tectum evoked by noxious stimulation. In separate experiments, the effects of noxious deep somatic and noxious visceral manipulations on arterial pressure and heart rate were measured. The noxious visceral manipulations evoked substantial and sustained falls in arterial pressure (15-45 mmHg), and heart rate (75-100 bpm), whereas the depressor and bradycardiac effects of the noxious deep somatic manipulations were weaker, not as sustained, or entirely absent. As similar distributions and numbers of both increased and decreased Fos-like IR cells were observed after each of the deep noxious manipulations, it follows that the deep noxious evoked increases and decreases in Fos expression were not secondary to the evoked depressor or bradycardiac effects.

Animals↗
PubMed1998

Gscl, a gene within the minimal DiGeorge critical region, is expressed in primordial germ cells and the developing pons.

Gscl, a paired-type homeobox gene, has been implicated in the pathology of DGS/VCFS by virtue of its genomic location and its structural similarity to the Gsc gene family. Immunohistochemical and in situ studies were performed to examine the expression pattern of this gene during embryonic development. A polyclonal antibody, generated to the full-length protein and shown to be specific for GSCL by both Western blotting and immunofluorescence, was used for immunohistochemical localization. Both in situ and antibody staining localized GSCL expression to a cluster of cells in the pons region of the developing brain. This GSCL expression pattern showed partial overlap with that of Pax6. More detailed immunohistochemistry revealed the GSCL in primordial germ cells during migration from the epithelium of the hindgut and later as they colonize the developing gonads. GSCL was not detected in tissues affected in DGS/VCSF.

3T3 Cells↗
PubMed2005

Spectrum of malformations of the hindbrain (cerebellum, pons, and medulla) in a cohort of children with high rate of parental consanguinity.

We review 25 patients with a spectrum of hindbrain (cerebellum, pons, and medulla) malformations from a cohort of children with high parental consanguinity rate. Twenty-three of the 25 patients were born to consanguineous parents. The patients were classified in four groups. Eleven patients of 6 families had malformation of the hindbrain and midbrain with molar tooth sign (10 patients of 5 families with typical Joubert syndrome), 5 patients showed severe supratentorial anomalies in addition to the hindbrain malformations, 5 patients had pontocerebellar or cerebellar hypoplasia with anterior horn cell disease in the spinal cord (spinal muscular atrophy), and 4 patients showed malformations affecting predominantly the hindbrain without substantial involvement of other systems. A locus for Joubert syndrome was previously identified on chromosome 9q34.3 in two families, and a second locus on chromosome 11p12-q13.3 in another family. A third Joubert syndrome locus has been mapped at 6q23 and a mutation in the AHI1 gene at this site has been found recently in a further family from this cohort. Delineation of homogeneous subgroups of patients with hindbrain malformations and molecular genetic analysis of these groups may lead to identification of further loci, genes and mutations responsible for the malformations.

Adolescent↗
PubMed2001

Differential expression of catecholamine synthetic enzymes in the caudal ventral pons.

The analysis of colocalization of multiple catecholamine biosynthetic enzymes within the ventrolateral part of the medulla oblongata of the rat revealed distinct subpopulations of neurons within the C1 region (Phillips et al., J Comp Neurol 2001, 432:20-34). In extending this study to include the caudal pons, it was shown for the first time that the A5 cell group could be distinguished by the presence of immunoreactivity to tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase (AADC), and dopamine beta hydroxylase (DBH). A novel cell group was also identified. The cells within this new group were immunoreactive to DBH but not TH, AADC, or phenylethanolamine N-methyltransferase (PNMT) and will be referred to as the TH-, DBH+ cell group. The TH-, DBH+ neurons were not immunoreactive for either the dopamine or noradrenaline transporters, suggesting that these neurons do not take up these transmitters. A5 neurons were immunoreactive for the noradrenaline transporter but not the dopamine transporter (as previously shown). Retrograde tracing with cholera toxin B revealed that the TH-, DBH+ neurons do not project to the thoracic spinal cord or to the rostral ventrolateral medulla, but A5 neurons do. A calbindin immunoreactive cell group is located in a region overlapping TH-, DBH+ cell group. However, only a few neurons were immunoreactive for both markers. The physiological role of the TH-, DBH+ cell group remains to be determined.

Animals↗