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C Bergeron

Publications and source records attributed to C Bergeron.

At least 163 records · Page 9Linked to original sources

Reduction of calbindin-28k mRNA levels in Alzheimer as compared to Huntington hippocampus.

Disturbances in calcium homeostasis have been observed to be associated with Alzheimer's and other neurodegenerative diseases. Increased total calcium levels and decreased levels of calcium binding proteins have been found in Alzheimer brain tissue. However, the mechanism behind these disturbances remain unknown. In situ hybridization with tritiated antisense RNA probes for the calcium binding proteins, calbindin-28k and calmodulin, was used to examine the expression of genes coding for these proteins in Alzheimer and Huntington brain tissues matched for age, agonal process and autopsy interval. mRNA levels for calbindin-28k were reduced by 35% in CA1 and CA2 regions of Alzheimer hippocampus, as compared to Huntington control. In contrast, calmodulin expression was unchanged in CA1 but reduced by 30% in CA2. mRNA expression of calbindin-28k and calmodulin in Alzheimer temporal cortex did not differ from control. There were no significant differences in calcium binding protein message levels in cerebellar Purkinje cells between Alzheimer and Huntington control. There was no correlation between calcium binding protein message levels and brain weight, autopsy interval, patient age or the extent of neurofibrillary degeneration. Instead, decreased calbindin-28k expression in Alzheimer-affected hippocampus was due to an increase in the percentage of neurons expressing lower message levels for these proteins.

Aged↗

Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment.

OBJECTIVE: To analyze the effects of clomiphene citrate (CC) on cervical mucus (CM) and endometrial morphology independently of hormonal changes encountered when CC is administered for ovulation induction. DESIGN: Volunteers whose ovarian functions were temporarily suppressed (n = 18) by a long-acting GnRH agonist and 6 women of similar age suffering from premature ovarian failure (POF) received E2 and P. Half of the women also received CC (50 mg/d, days 2 to 6). SETTING: Tertiary University Institution, Hôpital A. Béclère. PATIENTS, PARTICIPANTS: Eighteen volunteers suffering from infertility not related to a uterine cause and 6 women of similar age suffering from POF. MAIN OUTCOME MEASURE: Plasma gonadotropins, E2, and P were measured at baseline to confirm that the ovaries were inactive and twice weekly during physiological E2 and P replacement. Cervical mucus was analyzed on day 14 and scored from 0 to 15. Endometrial biopsies were obtained on replacement days 20 and 24 for conventional histology and immunocytochemistry analysis of estrogen receptors and progesterone receptors (PR). Premature ovarian failure women whose results have been previously published served as controls for day 20 biopsies. RESULTS: Cervical mucus scored lower in women who received CC (5.5 +/- 3.2) than in controls (13.6 +/- 4.7, mean +/- SEM). On day 20, endometrial findings were similar in women treated with CC and in controls. On day 24, specimens showed a significant delay in endometrial maturation in women treated with CC. On day 24, only staining for PR selectively persisted in endometrial stroma, and no difference was observed between women who received CC and controls. CONCLUSION: Our results indicate that CC significantly alters CM quality and late luteal phase endometrial morphology despite physiological levels of plasma E2 and P. Hence, clinicians should monitor E2 levels when using CC, and caution should be exerted when supraphysiological levels of E2 are not present to counterbalance the effects of CC on the CM and the endometrium.

Adult↗

Physiological oestradiol and progesterone replacement cycles in women with ovarian failure: a model to study endometrial maturation and sex steroid receptor regulation by exogenous hormones.

High endometrial receptivity has been achieved with physiological oestradiol and progesterone replacement cycles in women with ovarian failure. To understand whether different protocols using the oral route or the transdermal route can influence the endometrial maturation and the regulation of sex steroid receptors, we studied 33 women with ovarian failure treated by two commonly used protocols and assessed endometrial receptivity using light microscopy, scanning electron microscopy and immunohistochemistry for oestrogen and progesterone receptors on biopsies taken to include different periods of the luteal phase. The morphology in these patients was similar to that observed in women with normal ovulatory cycles, indicating that the morphological response is not dependent on the type of oestradiol, oral or transdermal, in the replacement cycles as compared to the endogenous oestradiol in the menstrual cycle. The relative distribution of steroid receptors between the epithelium and stroma varies similarly to that observed during the luteal phase of the menstrual cycle. These results confirm the role of progesterone, especially the importance of the number of days of exposure to it, in the disappearance of steroid receptors from endometrial glands. These observations give a better understanding of endometrial receptivity around the time of presumed implantation and confirm clinical results concerning the best timing of oocyte transfer.

Adult↗

Brain alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease.

We measured the activity of the alpha-ketoglutarate dehydrogenase complex (alpha-KGDHC), a rate-limiting Krebs cycle enzyme, in postmortem brain samples from 38 controls and 30 neuropathologically confirmed Alzheimer's disease (AD) cases, in both the presence and absence of thiamine pyrophosphate (TPP), the enzyme's cofactor. Statistically significant correlations between brain pH and lactate levels and alpha-KGDHC activity in the controls were observed, suggesting an influence of agonal status on the activity of alpha-KGDHC. As compared with the controls, mean alpha-KGDHC activity, with added TPP, was significantly (p < 0.005) reduced in AD brain in frontal (-56%), temporal (-60%), and parietal (-68%) cortices, with the reductions (-25 to -53%) in the occipital cortex, hippocampus, amygdala, and caudate failing to reach statistical significance. In the absence of exogenously administered TPP, mean alpha-KGDHC activity was reduced to a slightly greater extent in all seven AD brain areas (-39 to -83%), with the reductions now reaching statistical significance in the four cerebral cortical areas and hippocampus. A statistically significant negative correlation was observed between alpha-KGDHC activity and neurofibrillary tangle count in AD parietal cortex, the brain area exhibiting the most marked reduction in enzyme activity; this suggests that the enzyme activity reduction in AD brain may be related to the disease process and severity. In each brain area examined, TPP produced a greater stimulatory effect on alpha-KGDHC activity in the AD group (23-280% mean stimulation) as compared with the controls (-4 to +50%); this TPP effect could be explained by reduced endogenous TPP levels in AD brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Auto-immune idiopathic thrombocytopenic purpura in children. Apropos of 100 cases].

The authors report the results of a retrospective study concerning 100 children with immune thrombocytopenic purpura who were referred between January 1981 and January 1991. Twenty-seven children had a chronic evolution with a significantly high risk: girls aged 9 years or more, hospitalization longer than 10 days, or patients with a history of frequent ecchymoses. The risk of haemorrhage was highest at the early phase of the disease and when the platelet count was below 25 G/l. The need for laboratory tests has been controversial and the authors suggest a simplified list of tests after having demonstrated the limited value of tests attempting to document the prepurpuric infectious episode or associated disease. The number of responders was comparable in the group receiving corticosteroids (78%) and in that receiving intravenous immunoglobulins (76.5%), as was the number of complete remissions in both groups (40.4% and 50%, respectively). 20.5% of the patients receiving intravenous immunoglobulins experienced a chronic evolution versus 29.8% in the group receiving corticosteroids (no significant difference). Seventeen patients underwent splenectomy with excellent result, particularly in one child who underwent urgent splenectomy because of intracranial haemorrhage.

Adolescent↗

[Epidemiology of neuroblastoma in Brittany over a 10-year period (1980-1989)].

We report the results of a retrospective epidemiologic study on neuroblastoma in Brittany, a region of France characterized by an homogeneous sedentary population living on a granitic ground. During a period of 10 years (1980-1989), 48 cases of neuroblastoma were observed, which gives an incidence of 7.92 cases per million of children under 15 years. There were 25 boys and 23 girls and 20 infants under 1 year (41%). The localisation was abdominal in 39 cases (81%). Among the 28 children older than 1 year, 25 (89%) had stage III and stage IV neuroblastomas, half of them with metastases. We conclude that the incidence and the clinical presentation of neuroblastoma in Brittany are similar to those reported in other countries.

Child↗

Diencephalic idiopathic gliosis: an unusual hypothalamic syndrome of dermopathy, diarrhea and growth arrest.

This case report of a 16-year-old girl describes the association of chronic diarrhea and lower limb dermopathy with an unusual and widespread gliosis within hypothalamic and other diencephalic structures. This syndrome to our knowledge has not been previously reported. Hypothalamic disease was suggested during life by examination findings of sustained hypothermia, altered sleep-wake cycles and abnormal cortisol diurnal rhythms. Profound growth arrest from the age of 8 yr (growth velocity < 1.4cm/yr) despite normal levels of growth hormone and response to physiological stimuli were additional unusual features. Autopsy after sudden death at 16 yr showed extensive gliosis in hypothalamic and adjacent diencephalic structures with proportionately little neuronal loss--suggesting an unidentified stimulus to glial proliferation. In the absence of evidence of other organ dysfunction it is suggested that dermopathy and chronic diarrhea in this case may have an autonomic basis. The impaired tissue response to growth hormone could be due to chronic hypothermia or involvement of some other (unidentified) hypothalamic factor regulating growth velocity.

Adolescent↗

Reduction of vitamin D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: correlation with calbindin-28k mRNA levels.

Receptors for vitamin D hormone (VDR) and the calcium binding protein, calbindin-28k, have been localized in many tissues, including brain. In brain, VDR and calbindin-28k were reported to colocalize in hippocampal CA1 cells. We have shown that mRNA pool size for calbindin-28k was reduced, on average, by 35% in Alzheimer hippocampal CA1 cells, as compared to Huntington control (manuscript in preparation). In the present study, in situ hybridization with tritiated antisense RNA probes was used to examine VDR expression in paired Alzheimer and Huntington brain tissue. Message levels for VDR were reduced, on average, by 34% and 31%, respectively, in Alzheimer hippocampal CA1 and CA2 pyramidal cells, as compared to Huntington control. However, VDR message levels were not significantly different from control in Alzheimer temporal cortex or cerebellum. There was no correlation between VDR message levels and brain weight, autopsy interval, patient age or the extent of neurofibrillary degeneration. Instead, VDR mRNA pool size in hippocampal CA1 cells correlated significantly with calbindin-28k message levels (r = 0.52, P less than 0.001). Decreased message levels for VDR and calbindin-28k in these cells were due to an increased percentage of cells expressing lower message levels for these proteins. These results show that in Alzheimer hippocampal CA1 cells, VDR mRNA pool size is downregulated and that this downregulation may play a role in the reduction of calbindin-28k expression.

Alzheimer Disease↗

Effects of experimental conditions on the production of interleukin-1 alpha and -1 beta by human endothelial cells cultured in vitro.

We have characterized the production of IL-1 alpha and -beta in primary and passaged cultures of quiescent human umbilical vein endothelial cells (HUVECs) using highly specific and sensitive solid-phase enzyme immunoassays. Primary cultures produced both immunoreactive IL-1 alpha and IL-1 beta following stimulation with lipopolysaccharide with the alpha form predominating over the beta. Most of the IL-1 produced remained cell-associated. Primary, but not passaged, cultures were significantly contaminated by macrophage-like cells, possibly accounting for higher production of IL-1, especially IL-1 beta. Gel filtration of secreted proteins derived from cultured HUVECs showed that the immunoreactive IL-1 alpha exhibited the expected molecular weight (17 kDa), but cell-associated IL-1s appeared to be a mixture of the 17 kDa protein and of higher molecular weight precursors. Mitogens in the culture medium (serum and endothelial cell growth supplement) were powerful stimuli of endothelial IL-1 production and accounted for the relatively high basal IL-1 levels observed in the cultured endothelial cells. The proliferative phenotype of the endothelium is possibly linked to the expression of high level of IL-1, which until now was thought to be an autocrine inhibitor of endothelial cell mitosis.

Cells, Cultured↗

Human papillomaviruses associated with cervical intraepithelial neoplasia. Great diversity and distinct distribution in low- and high-grade lesions.

All together, 30 genital human papillomavirus (HPV) types have been characterized so far. To evaluate the importance of HPV diversity in associated cervical diseases, we analyzed 188 biopsy specimens obtained from patients with a recent diagnosis of cervical HPV infection or intraepithelial neoplasia (CIN). Of these 188 specimens, 116 were classified as low-grade CIN (48 cases), high-grade CIN (53 cases), condylomata acuminata (10 cases), flat condylomas (five cases). Seventy-two specimens were considered nondiagnostic. Using probes specific for 18 genital HPV types, HPV DNA sequences were detected by Southern blot hybridization in 100 lesions and 21 nondiagnostic specimens. When further analyzed by the polymerase chain reaction, eight HPV-negative biopsy specimens, four CIN, and four nondiagnostic specimens were positive. Of the 129 positive biopsy specimens, 92 contained at least one of 18 known HPV types and 37 HPV that have not yet been identified. Nine specimens had more than one type. Thirteen HPV types were identified in CIN. The detection rate of HPV 16 increased from 21% in low-grade CIN to 57% in high-grade CIN. HPV 18 was detected in only 3% of CIN; HPV 31, 33, and 35 were found in 8%. HPV 30, 39, 45, 51, 52, 56, 58, and 61 were detected in 44% of low-grade CIN but in only 8% of high-grade CIN. Unidentified HPV were detected in about 25% of low-grade and high-grade CIN. Fifty-seven CIN positive for at least one HPV type were further analyzed by in situ hybridization. Thirty-five (65%) biopsy specimens were positive, including 21 of 24 low-grade CIN and 14 of 33 high-grade CIN. Ten of the 13 previously identified HPV types were detected. Thus, CIN represents an heterogeneous disease from a virologic viewpoint. This fact could explain their variable clinical evolution.

Adolescent↗

Brain cytochrome oxidase in Alzheimer's disease.

A recent demonstration of markedly reduced (-50%) activity of cytochrome oxidase (CO; complex 4), the terminal enzyme of the mitochondrial enzyme transport chain, in platelets of patients with Alzheimer's disease (AD) suggested the possibility of a systemic and etiologically fundamental CO defect in AD. To determine whether a CO deficiency occurs in AD brain, we measured the activity of CO in homogenates of autopsied brain regions of 19 patients with AD and 30 controls matched with respect to age, postmortem time, sex, and, as indices of agonal status, brain pH and lactic acid concentration. Mean CO activity in AD brain was reduced in frontal (-26%: p less than 0.01), temporal (-17%; p less than 0.05), and parietal (-16%; not significant, p = 0.055) cortices. In occipital cortex and putamen, mean CO levels were normal, whereas in hippocampus, CO activity, on average, was nonsignificantly elevated (20%). The reduction of CO activity, which is tightly coupled to neuronal metabolic activity, could be explained by hypofunction of neurons, neuronal or mitochondrial loss, or possibly by a more primary, but region-specific, defect in the enzyme itself. The absence of a CO activity reduction in all of the examined brain areas does not support the notion of a generalized brain CO abnormality. Although the functional significance of a 16-26% cerebral cortical CO deficit in human brain is not known, a deficiency of this key energy-metabolizing enzyme could reduce energy stores and thereby contribute to the brain dysfunction and neurodegenerative processes in AD.

Aged↗

Detergent-insoluble cortical Lewy body fibrils share epitopes with neurofilament and tau.

Lewy bodies are cytoskeletal inclusions associated with neuronal injury and death in idiopathic Parkinson's disease and other neurodegenerative disorders. The chemical composition of the 8-10-nm fibrils of the Lewy body is unknown, although they are related to both normal cytoskeletal elements and paired helical filaments of Alzheimer neurofibrillary tangles. From the Lewy body-rich cerebral cortex of patients with diffuse Lewy body disease we have isolated intact Lewy bodies using a high salt buffer/nonionic detergent gradient centrifugation procedure and extracted the constitutive fibrils with urea and sodium dodecyl sulfate. Urea/detergent-resistant Lewy body fibrils were solubilized with formic acid and found to contain a single protein band of 68 kDa, which was not found in identically prepared normal brain homogenates. The Lewy body derived-polypeptide was recognized on immunoblots by a polyclonal antibody that reacted with both the 68-kDa neurofilament subunit and the microtubule-associated protein tau. The 68-kDa Lewy body protein was not labeled by the monoclonal antibody tau-1 despite prior in vitro enzymatic dephosphorylation. We conclude that the detergent-insoluble component of the cortical Lewy body fibril shares epitopes with neurofilament and tau and may be a posttranslationally modified derivative of either neurofilament or tau with substantially altered biochemical and immunologic properties.

Amino Acids↗

Alloimmune thrombocytopenia: in utero treatment by high doses of intravenous gamma globulins.

The authors report successful in utero treatment by high doses of intravenous gamma globulins in a case of neonatal alloimmune thrombocytopenia. Early diagnosis allows an appropriate management: fetal blood sampling as early as 20 weeks of gestation; in case of fetal thrombocytopenia, treatment by intravenous gamma globulin (1.0 g/kg/b.w.) each week during 8 weeks or more; ultrasound screening of in utero hemorrhage, particularly intracranial hemorrhage; fetal blood sampling before delivery at term and in utero transfusion of platelet antigen negative in case of persistence of fetal thrombocytopenia.

Adult↗

Effects of luteal estradiol on the secretory transformation of human endometrium and plasma gonadotropins.

To study the role of luteal estradiol (E2), we interrupted the supply of E2 during the luteal phase of E2 and progesterone (P) replacement cycles. Thirty-one women, aged 26-37 yr, with absent or inactive ovaries received three different treatment regimens: group I (n = 11) received transdermal E2 and vaginal P according to a protocol designed to approximate levels of estrone (E1), E2, and P seen during the menstrual cycle. Groups II (n = 11) and III (n = 9) received identical treatments, except that in group II no E2, and in group III no E2 or P, was administered after day 15. Endometrial biopsies were obtained on days 20 and 24 in groups I and II, and on days 14 and 20 in group III. In group I, plasma E1 and E2 reached menstrual cycle levels, whereas in groups II and III, discontinuation of the E2 supply on day 15 resulted in a prompt decrease to castrate levels of plasma E1 and E2. In groups I and II, menopausal FSH and LH levels decreased to 26 +/- 6 and 30 +/- 7 IU/L, respectively, on day 13 (mean +/- SEM). In group I, administration of E2 and P starting on day 15 further lowered plasma gonadotropin levels. In group II, administration of P only failed to induce a similar decrease in plasma FSH and LH. No uterine bleeding occurred before day 25 in women of groups I or II, while women of group III bled within 2 days of E2 withdrawal. Endometrial biopsies were similar in groups I and II. Histological features were characteristic of early and late luteal phases on days 20 and 24, respectively. Endometrial maturation assessed by estrogen and progesterone receptors identified by immunocytochemistry showed the typical distribution seen on day 24 of the menstrual cycle with no difference between groups I and II. We conclude that in women deprived of ovarian function, administration of P only after 14 days of E2 priming prevented uterine bleeding and induced normal secretory transformations of the endometrium, but failed to suppress plasma gonadotropins.

Administration, Cutaneous↗

Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene.

We present prospective clinical and neuropathologic details of a pedigree segregating familial Alzheimer's disease (FAD) associated with a mutation (G----A substitution) at nucleotide 2149 in exon 17 of the amyloid precursor protein (APP) gene. This mutation, which is predicted to cause the missense substitution of isoleucine for valine at codon 717 of APP, cosegregated perfectly with the FAD trait (lod score = 3.49 at theta = 0.00). The earliest clinical manifestations of the disease relate to deficits in memory function, cognitive processing speed, and attention to complex cognitive sets. These changes occurred in the absence of changes in nonmemory language and visuospatial functions. The neuropathologic features of FAD associated with the APP717 mutation in this family include severe neuronal loss, abundant neurofibrillary tangles, amyloid plaques, and amyloid angiopathy. These results provide independent confirmation that mutations in the APP gene are linked to the FAD trait in some families.

Adult↗