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K G Petry

Publications and source records attributed to K G Petry.

At least 19 recordsLinked to original sources

In vivo evaluation of remyelination in rat brain by magnetization transfer imaging.

The aim of this work was to assess quantitatively and qualitatively the ability of magnetization transfer imaging to follow in vivo remyelination. Demyelination lesions were induced in rats by the injection of L-alpha-lysophosphatidylcholine stearoyl into the corpus callosum and imaging was performed in vivo on a 4.7-Tesla system at different time points. The percentage of magnetization transfer ratio (MTR) decrease was calculated for each animal. To evaluate the MTR findings for remyelination, myelin was quantitated by histological analysis of the lesion size and counting the number of remyelinating axons. An MTR decrease was observed when demyelination was present at 7 days after injection. During the remyelinating phase between day 30 and 40 after injection, contralateral values almost complete returned to normal, thus indicating remyelination. Histologically, at days 30 and 40 after injection, the lesion area was reduced in size and the axons were surrounded by a thin myelin sheath, indicating the remyelination process. Statistical analysis showed that the profile of MTR values was significantly correlated with the course of remyelination. All the MTR changes show a correlation with both myelin damage and repair. In conclusion, the study of the MTR profile in this myelin lesion model demonstrates in vivo the loss of myelin and the presence of spontaneous remyelination. This methodological approach which can also be applied to multiple sclerosis patients to show demyelination, should prove helpful to determine the degree of spontaneous and therapeutically induced remyelination in multiple sclerosis lesions, and thus to validate therapeutic treatments for myelin repair.

Animals↗

Experimental allergic encephalomyelitis animal models for analyzing features of multiple sclerosis.

Various animal models with experimental allergic encephalomyelitis (EAE) have been developed applying immunologic, virologic, toxic and traumatic parameters in order to understand features of multiple sclerosis (MS). The main simulating aspects of the EAE models and the precautions for their interpretation in determining differences and common features between EAE and MS are presented. In view of an early diagnosis of CNS lesions in human, we present with particular interest the application of human-related technologies, such as MR imaging techniques, and the development of new markers to follow the dynamic of CNS lesions in vivo in EAE animal models.

Animals↗

A protein with the characters of a zinc-finger is implicated in the differentiation of Schwann cells.

During the development of the PNS, Schwann cells (SC) differentiate into myelinating and nonmyelinating cells, implying regulation by different transcription factors such as ZF proteins. Employing an original strategy using monoclonal antibodies specifically directed against the conserved ZF motif, we have identified a new ZF protein of 55 kDa present in rat sciatic nerve extract (SCp55). We used polyclonal antibodies and cloned cDNA to characterize the expression of SCp55 by immunohistochemistry and in situ hybridization. This protein is specific for SC and shows differential expression both during development and between the two SC phenotypes. When they differentiate the protein is first induced in myelinating SC and then in nonmyelinating SC. The nature of this protein together with its differential expression suggests that it is a transcription factor that may have a role in the development of SC.

Amino Acid Sequence↗

Dose and scanning delay using USPIO for central nervous system macrophage imaging.

RATIONALE AND OBJECTIVES: In experimental allergic encephalomyelitis (EAE), central nervous system (CNS) macrophage imaging is achievable by MRI using AMI-227 an ultra-small particle iron oxide contrast agent at a dose of 300 micromol/kg Fe. The objective was to test the feasibility at the human recommended dose of 45 micromol/kg Fe. METHODS: Two groups of EAE rats were tested with AMI-227 using 45 and 300 micromol/kg Fe respectively. Following i.v. injection of AMI-227, they were scanned after a delay of 4-6 and 20-24 h. RESULTS: With a high dose of AMI-227, all animals showed low signal intensity related to iron-loaded macrophages in the CNS. At low dose no abnormalities were found in the CNS. Furthermore, a delay of 4-6 h failed to demonstrate abnormalities even at high dose. CONCLUSIONS: Dose, scanning delay after administration and blood half-life are major parameters for T2* CNS macrophage imaging.

Animals↗

Adrenalectomy increases neurogenesis but not PSA-NCAM expression in aged dentate gyrus.

Ageing is accompanied by a decline in neurogenesis and in polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) expression within the hippocampus and by elevated basal levels of circulating corticosterone. In a companion study, we demonstrated that suppression of corticosterone by adrenalectomy increased neurogenesis and PSA-NCAM expression in the dentate gyrus of adult rats. Here we show that adrenalectomy increased neurogenesis in this structure in old rats, as measured by the incorporation of 5-bromo-2'-deoxyuridine in neuronal progenitors. This effect was prevented by corticosterone replacement. In contrast, PSA-NCAM expression remained unchanged in comparison with controls. Thus, in the aged brain, stem cells are still present and able to enter the cell cycle. This may point to ways of protecting or treating age-related cognitive impairments.

Adrenal Glands↗

Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis.

BACKGROUND AND PURPOSE: Ultrasmall particles of iron oxide (USPIO) constitute a contrast agent that accumulates in cells from the mononuclear phagocytic system. In the CNS they may accumulate in phagocytic cells such as macrophages. The goal of this study was to compare USPIO-enhanced MR images with conventional T2-weighted images and gadolinium-enhanced T1-weighted images in a model of experimental autoimmune encephalomyelitis (EAE). METHODS: Nine rats with EAE and four control rats were imaged at 4.7 T and 1.5 T with conventional T1- and T2-weighted sequences, gadolinium-enhanced T1-weighted sequences, and T2-weighted sequences obtained 24 hours after intravenous injection of a USPIO contrast agent, AMI-227. Histologic examination was performed with hematoxylin-eosin stain, Perls' stain for iron, and ED1 immunohistochemistry for macrophages. RESULTS: USPIO-enhanced images showed a high sensitivity (8/9) for detecting EAE lesions, whereas poor sensitivity was obtained with T2-weighted images (1/9) and gadolinium-enhanced T1-weighted images (0/9). All the MR findings in the control rats were negative. Histologic examination revealed the presence of macrophages at the site where abnormalities were seen on USPIO-enhanced images. CONCLUSION: The high sensitivity of USPIO for macrophage activity relative to other imaging techniques is explained by the histologic findings of numerous perivascular cell infiltrates, including macrophages, in EAE. This work supports the possibility of intracellular USPIO transport to the CNS by monocytes/macrophages, which may have future implications for imaging of human inflammatory diseases.

Animals↗

Differential UDP-galactose-4'-epimerase (GALE) enzymatic activity and mRNA expression in the rat mammary gland during lactation.

We have investigated the UDP-galactose-4'-epimerase (GALE) enzymatic activity and mRNA expression in the rat mammary gland during lactation. We report a dramatic increase in the GALE enzymatic activity correlated with an increase in the mRNA transcript expression. These results indicate a transcriptional regulation of the enzyme during lactation in the rat mammary gland. Our data are of double interest for further investigation: first, the mammary gland provides a suitable model for the characterisation of the transcriptional regulation elements of GALE which are still unknown in mammals; second, GALE expression could help to compensate UDP-galactose deficiency in classic galactosaemia.

Animals↗

The fundamental importance of human galactose metabolism: lessons from genetics and biochemistry.

Cloning and characterization of all three human galactose-metabolic genes (GALK, GALT and GALE) has led to the identification of a number of mutations which are generally of the missense type in patients with galactosemia, an inborn error of metabolism. The predominance of missense mutations is interesting, considering the general importance of galactose metabolism for cellular energy production and proper modification of glycoproteins and glycolipids. Abnormalities in both of these macromolecules have been described in transferase-deficiency galactosemia, the most common and best-studied form of galactosemia. Thus, the parallel biochemical and molecular genetic analyses of human galactose metabolism are shedding light on this under-appreciated metabolic pathway that is critical for cellular energy production, modification of cellular macromolecules and normal human development.

Carbohydrate Sequence↗

Complex regulation of the expression of the polysialylated form of the neuronal cell adhesion molecule by glucocorticoids in the rat hippocampus.

The gyrus dentatus is one of the few areas of the brain that continues to produce neurons after birth. The newborn cells differentiate into granule cells which project axons to their postsynaptic targets. This step is accompanied by the transient expression of the polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM) by the developing neurons. Glucocorticoid hormones have been shown to inhibit neurogenesis. We noted a functional correlation between PSA-NCAM expression and glucocorticoid action after manipulation of corticosterone levels in the adrenalectomized rat. Adrenalectomy increased neurogenesis, evaluated from the incorporation of 5-bromo-2'-deoxyuridine in neuronal precursors, as well as PSA-NCAM expression. The increase in PSA-NCAM-immunoreactive (IR) cells in the gyrus dentatus, evidenced 72 h following adrenalectomy, persisted for at least a month. It was accompanied by enhanced dendritic arborization of PSA-NCAM-IR cells in the gyrus dentatus and by an increase in number of PSA-NCAM-IR fibres in the CA3 subfield. Neurogenesis was normalized by restitution of diurnal or nocturnal levels of corticosterone, whereas normalization of PSA-NCAM expression was only observed after simulation of the complete circadian fluctuation of the hormone. Our findings reveal the complex action of corticosterone in modulating the expression of PSA-NCAM in the gyrus dentatus of the hippocampal formation. They also highlight the importance of corticosterone fluctuations in the control of neurogenesis and plasticity in this structure.

Adrenalectomy↗

Decrease in highly polysialylated neuronal cell adhesion molecules and in spatial learning during ageing are not correlated.

Age-dependent spatial memory impairments have been related to a decline in hippocampal plasticity. Highly polysialylated neuronal cell adhesion molecules (PSA-NCAM) show a strong expression during adulthood within regions associated with neuroplastic events. Furthermore, NCAM molecules have been proposed to mediate neuronal plasticity during learning and memory. The aim of the present study was to examine the effect of ageing on the expression of PSA-NCAM within the hippocampus. To investigate whether age-dependent changes in expression of PSA-NCAM were accentuated in aged rats with learning impairment, animals were in a first step assessed for their cognitive abilities using a Morris water maze. Seven-month-old and 24-month-old-rats were tested for their performance in the Morris water maze. The animals were sacrificed and brain sections were processed for PSA-NCAM immunohistochemistry. Ageing was accompanied by an overall decrease in PSA-NCAM-immunoreactivity (-IR) within the forebrain, presenting a important decrease of the number of PSA-NCAM-IR perikarya within the hippocampus. These results were confirmed by Western blot analysis. No difference in PSA-NCAM immunoreactivity was observed in aged rats with or without spatial learning impairment. It is concluded that although changes in PSA-NCAM accompanied the decrease in cognitive abilities, our data did not evidence a causal relationship between these two parameters.

Aging↗

Altered follicle stimulating hormone isoforms in female galactosaemia patients.

UNLABELLED: Many women affected with galactosaemia suffer from ovarian dysfunction and have elevated serum levels of follicle stimulating hormone (FSH). We have analysed FSH-glycoprotein isoforms from four galactosaemic and five healthy women. Besides the commonly found FSH species with a median isoelectric point (pI) of 4-5, the sera of the female galactosaemic patients contained qualitatively abnormal FSH isoforms with a pI close to neutral (6.4-7.0). The generally reduced galactosylation in patient samples was confirmed because sera of galactosaemic patients could incorporate 1.7 times more UDP-(14C)galactose than did healthy subjects. CONCLUSION: Our data indicate that the terminal disaccharides of FSH (a glycoprotein), galactose and sialic acid were partially deficient in three galactosaemic female patients with no galactose-1-phosphate uridyl transferase (GALT) activity in red cells. However, from a female patient with a residual GALT activity (a mild form of galactosaemia), no distinctive deficiency was observed. This again suggest an importance of GALT in retaining a correct FSH structure. Therefore the abundance of neutral FSH isoforms, which was described to have a higher binding affinity to its receptor and no capacity to activate cyclic adenosine mono-phosphate (cAMP), may cause a hormonal dysfunction in classical galactosaemia.

Adolescent↗

Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.

A model was developed to study inhibitors present in feces which prevent the use of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with the same primers as H. pylori was used to spike samples before extraction by a modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column, were characterized. Inhibitors in feces are complex polysaccharides possibly originating from vegetable material in the diet.

Feces↗

Three different anti-myelin antibodies in a case of demyelinating dysglobulinemic peripheral neuropathy.

We report the case of a patient with a severe, predominantly motor, demyelinating neuropathy associated with an IgM kappa biclonal gammopathy. Immunoblot studies showed IgM reactivity against MAG, and IgG reactivity against a peripheral nerve myelin-specific protein of approximately 35 kDa. Immunodetection by thin layer chromatography showed IgM reactivity towards GM1 and GD1b, as well as towards SGPG and SGLPG. This case illustrates the existence of overlapping syndromes among dysglobulinemic neuropathies, and points to an interaction of different autoantibodies in the pathogenesis of the nerve lesions.

Aged↗

In vivo and in vitro expression of rat galactose-1-phosphate uridyltransferase (GALT) in the developing central and peripheral nervous system.

Galactose-1-phosphate uridyltransferase (GALT) is a key enzyme in the metabolism of galactose. GALT activates the galactose-glucose interconversion and enables the synthesis of glucose-1-phosphate and UDP-galactose (UDP-Gal). UDP-Gal is the galactosyl donor for the incorporation of galactose into complex oligosaccharides, glycoproteins and glycolipids. The expression of GALT was characterized both in vivo and in vitro during late embryonic and postnatal development of the brain and peripheral nerve of the rat. Assays of GALT mRNA and protein showed that it is weakly expressed during late embryonic development with a second peak of expression concomitant with myelinogenesis. GALT was prominently expressed in myelinating Schwann cells in a rat dorsal root ganglia culture system. GALT deficiency in humans results in galactosemia, a disease characterized by long-term intellectual impairment, and probably dysmyelination. The developmentally regulated pattern of GALT expression during maturation of the nervous system may provide a molecular basis for these neurological complications which seriously compromise the outcome of many galactosemic patients.

Animals↗

Circulating antibodies directed against conjugated fatty acids in sera of patients with multiple sclerosis.

Using an adapted ELISA assay, we have tested sera from multiple sclerosis (MS) patients for antibodies directed against ten fatty acids conjugated to bovine serum albumin. In serum samples from 68 MS patients and 20 patients suffering from rheumatoid arthritis (RA), a significant antibody titer elevation to the ten tested fatty acids was found when compared to sera of 40 healthy subjects and 82 patients with other neurological and autoimmune diseases. G-200 purified IgM of MS patients reacted specifically with the aliphatic chains with an avidity of 3 x 10(-7) M. These results suggest that in MS and RA, autoepitopes on cell membranes that are normally hidden from the immune system become immunogenic. This may arise because of previous membrane disruption by oxidative processes.

Adult↗

Expression of galactose-1-phosphate uridyltransferase in the anterior pituitary of rat during the estrous cycle.

Biological activity of the follicle-stimulating hormone (FSH) is dependent on its pattern of glycosylation and is altered during galactosemia, a genetic disease characterized by deficient activity of galactose-1-phosphate uridyltransferase (GALT). To assess the role of this enzyme in the synthesis of FSH, the expression of GALT at the mRNA and protein levels was measured in the whole anterior pituitary during the estrous cycle of rat. GALT was maximally expressed during the proestrous and estrous phases of the estrous cycle. The expression pattern of GALT was associated with gonadotropin-expressing cells. This close association is in accordance with the postulated role of GALT in modulating biological activity of FSH.

Animals↗