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Biomedical subjects

C Bernard

Publications and source records attributed to C Bernard.

At least 19 recordsLinked to original sources

Symptomatic splenic hamartoma with renal, cutaneous, and hematological abnormalities.

BACKGROUND: There is a rare association between splenic hamartomas and hematological abnormalities with, to our knowledge, only 24 reported cases in the English literature. PATIENTS AND METHODS: We report a case of a splenic hamartoma in a 14-year-old boy associated with membranoproliferative glomerulonephritis, multiple lobular capillary hemangiomas of the skin, hypertension, and anemia. Following imaging with ultrasonography, MRI, and nuclear scans, a hamartoma was suspected, but malignancy could not be excluded. The lesion was removed by partial splenectomy, and pathological examination confirmed the presence of a red pulp splenic hamartoma. RESULTS: The renal, hematological, and dermatological abnormalities resolved following removal of the splenic hamartoma. This is the first reported case of a splenic hamartoma associated with renal, cutaneous, and hematological abnormalities and only the second reported case of a symptomatic splenic hamartoma treated by partial splenectomy.

Adolescent↗

Presynaptic kainate receptors that enhance the release of GABA on CA1 hippocampal interneurons.

We report that kainate receptors are present on presynaptic GABAergic terminals contacting interneurons and that their activation increases GABA release. Application of kainate increased the frequency of miniature inhibitory postsynaptic currents recorded in CA1 interneurons. Local applications of glutamate but not of AMPA or NMDA also increased GABA quantal release. Application of kainate as well as synaptically released glutamate reduced the number of failures of GABAergic neurotransmission between interneurons. Thus, activation of presynaptic kainate receptors increases the probability of GABA release at interneuron-interneuron synapses. Glutamate may selectively control the communication between interneurons by increasing their mutual inhibition.

Animals↗

Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy.

Impaired inhibition is thought to be important in temporal lobe epilepsy (TLE), the most common form of epilepsy in adult patients. We report that, in experimental TLE, spontaneous GABAergic inhibition was increased in the soma but reduced in the dendrites of pyramidal neurons. The former resulted from the hyperactivity of somatic projecting interneurons, whereas the latter was probably due to the degeneration of a subpopulation of dendritic projecting interneurons. A deficit in dendritic inhibition could reduce seizure threshold, whereas enhanced somatic inhibition would prevent the continuous occurrence of epileptiform activity.

Action Potentials↗

Purine and pyrimidine nucleotide-sensitive phospholipase A(2) in ampulla from frog semicircular canal.

This study was attempted to characterize pharmacologically the P2Y receptors triggering phospholipase A(2) (PLA(2)) activation in ampulla from frog semicircular canal. A microassay was developed to screen the abilities of UTP analogs to stimulate [(3)H]arachidonic acid release by labeled ampullas. At 26 degrees C UTP induced a dose-dependent and saturable increase of PLA(2) activity (apparent activation constant 1.3 +/- 0.4 microM, Hill coefficient 0.9 +/- 0.2, maximal stimulating factor 2.0 +/- 0.1). The rank order of potency of agonists for PLA(2) activation was UTP > or = UDP > adenosine 5'-O-(2-thiodiphosphate) = adenosine 5'-O-(3-thiotriphosphate) > or = ATP = 2-methylthio-ATP > or = ADP = diadenosine tetraphosphate > or = alpha,beta-methylene-ATP = CTP > 2' and 3'-O-(4-benzoylbenzoyl)-ATP > or = AMP = UMP >> uridine and adenosine. UTP- and 2-methylthio-ATP-induced PLA(2) activations were inhibited by U-73122, GF-109203X, and methyl arachidonyl fluorophosphate. Basal activity was stimulated by phorbol ester and epinephrine and reduced by vasotocin, isoproterenol, prostaglandin E(2), cAMP, and forskolin. H-89 restored the cAMP- and forskolin-inhibited PLA(2) activities. Results indicate that P2Y receptor-mediated PLA(2) stimulation requires phopholipase C and protein kinase C activations and basal activity is inhibited by agonist-stimulated cAMP-dependent mechanisms.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Peptones stimulate intestinal cholecystokinin gene transcription via cyclic adenosine monophosphate response element-binding factors.

Cholecystokinin (CCK) is a potent intestinal hormone that regulates several digestive functions. Despite the physiological importance of CCK, the cellular and molecular mechanisms that govern its synthesis and secretion are not completely identified. Peptones, which are fair counterparts of the protein fraction in the intestinal lumen, are good stimulants of CCK secretion. We have previously shown that peptones activate CCK gene transcription in STC-1 enteroendocrine cells. The DNA element(s) necessary to induce the transcriptional stimulation was preliminary, localized in the first 800 bp of the CCK gene promoter. In the present study, we identify a DNA element [peptone-response element (PepRE)] essential to confer peptone-responsiveness to the CCK promoter, and we characterize the transcription factors implicated. Localization of the PepRE between -93 and -70 bp of the promoter was established using serial 5'-3'deletions. Systematic site-directed mutagenesis demonstrated that the core PepRE sequence, spanning from nucleotide -72 to -83, overlapped with the putative AP-1/CRE site. Mutations in the core sequence dramatically decreased peptone-responsiveness of CCK promoter fragments. The PepRE functioned as a low-affinity CRE consensus site, binding only transcription factors of the CREB family. Overexpression, in STC-1 cells, of a dominant-negative protein (A-CREB), that prevented the binding of CREB factors to DNA, completely abolished the peptone-induced transcriptional stimulation. Peptone treatment did not modify the nature and the abundance of proteins bound to the PepRE but led to increased phosphorylation of the CREB factors. In conclusion, the present study first demonstrates that CCK gene expression is under the control of protein-derived nutrients in the STC-1 enteroendocrine cell line.

Animals↗

Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload.

The cardiac LIM domain protein MLP plays a crucial role in the architecture and mechanical function of cardiac myocytes. Mice lacking the MLP gene develop cardiac hypertrophy, dilated cardiopathy and heart failure. We investigated whether downregulation of MLP is induced by pressure overload and contributes to the physiopathology of cardiac hypertrophy and failure. We studied this mechanism in rat right ventricles submitted to pulmonary arterial hypertension, because it is known that this ventricle is very vulnerable to the deleterious effects of pressure overload. During the progression of cardiac hypertrophy to failure over a 31 days period there was a dramatic decrease by 50% of the MLP transcripts level. Consistently, immunohistochemistry detected very weak protein signals in the cytoplasms of cardiomyocytes at the failing stage, but myocytes nuclei were heavily labeled. The nuclear relocation was confirmed by the immunodetection of MLP on the nuclear and cytosolic fractions. This nuclear localization is the hallmark of a retro-differentiated phenotype, since it has been observed only in differentiating myoblasts. These changes were associated with ultrastructural disorganization of the myofibrils similar to that observed in MLP -/- mice. Therefore, MLP dowregulation occurring during gene reprogramming may critically contribute to mechanical failure of the myocardium.

Animals↗

Cow's-milk-induced allergic colitis in an exclusively breast-fed infant: diagnosed with ultrasound.

BACKGROUND: An exclusively breast-fed-8-week-old boy presented with irritability and non-bilious projectile vomiting. He was referred to our Medical Imaging Department to eliminate pyloric stenosis. PATIENT AND METHODS: A diagnosis of colitis was strongly suggested by ultrasound. A more detailed history revealed that the patient also had episodes of colicky pain and bloody stools. An infectious colitis was subsequently excluded and rectal biopsy supported the diagnosis of allergic proctocolitis. RESULTS: The infant responded well to the withdrawal of cow's milk and dairy products from the maternal diet. CONCLUSION: Allergic proctocolitis should be included in the differential diagnosis of infants presenting with vomiting and/or bloody stools.

Animals↗

Site-specific epithelial-mesenchymal interactions in digestive neuroendocrine tumors. An experimental in vivo and in vitro study.

Little is known about the functional interactions between digestive neuroendocrine tumor cells and their stromal microenvironment. The focus of our study is whether mesenchymal cells modulate peptide expression, cell proliferation, and invasiveness in digestive neuroendocrine tumor cells. We designed an experimental in vivo and in vitro study using the mouse enteroendocrine cell line STC-1. In vivo, STC-1 cells were injected subcutaneously in 18 immunosuppressed newborn rats. At day 21, all animals presented poorly differentiated neuroendocrine tumors with lung metastases. Subcutaneous tumors were usually limited by a capsule containing basement membrane components and myofibroblasts that presented a low mitotic index. Lung tumors were devoid of capsule and poor in myofibroblasts, and their mitotic index was high. The profile of peptide expression in STC-1 tumors was different from that of cultured STC-1 cells. In vitro, STC-1 cells were cultured with fibroblasts of different origins, including dermis, lung, digestive tract, and liver. Based on their origin, myofibroblasts differentially modulated hormone synthesis, proliferation, spreading, and adhesion of STC-1 cells. In conclusion, our results show that site-specific functional interactions between mesenchymal and neuroendocrine cells may contribute to modulating the behavior of digestive neuroendocrine tumors, depending on their growth site.

Animals↗

Distribution of spontaneous currents along the somato-dendritic axis of rat hippocampal CA1 pyramidal neurons.

Excitatory and inhibitory pathways have specific patterns of innervation along the somato-dendritic axis of neurons. We have investigated whether this morphological diversity was associated with variations in the frequencies of spontaneous and miniature GABAergic and glutamatergic synaptic currents along the somato-dendritic axis of rat hippocampal CA1 pyramidal neurons. Using in vitro whole cell recordings from somata, apical dendrites and basal dendrites (for which we provide the first recordings) of CA1 pyramidal neurons, we report that over 90% of the spontaneous currents were GABAergic, <10% being glutamatergic. The frequency of spontaneous GABAergic currents was comparable in the soma and in the dendrites. In both somata and dendrites, the Na(+) channel blocker tetrodotoxin abolished more than 80% of the spontaneous glutamatergic currents. In contrast, tetrodotoxin abolished most dendritic (>90%) but not somatic (<40%) spontaneous GABAergic currents. Computer simulations suggest that in our experimental conditions, events below 40pA are electrotonically filtered to such a degree that they are lost in the recording noise. We conclude that, in vitro, inhibition is massively predominant over excitation and quantitatively evenly distributed throughout the cell. However, inhibition appears to be mainly activity-dependent in the dendrites whereas it can occur in the absence of interneuron firing in the soma. These results can be used as a benchmark to compare values obtained in pathological tissue, such as epilepsies, where changes in the balance between excitation and inhibition would dramatically alter cell behaviour.

Action Potentials↗

Effective therapy for severe Henoch-Schonlein purpura nephritis with prednisone and azathioprine: a clinical and histopathologic study.

OBJECTIVES: To validate a scoring system to assess the severity of renal lesions and to correlate histology with clinical findings. We also examined the efficacy of treatment with prednisone (1 to 2 mg/kg/d) and azathioprine (1 to 2 mg/kg/d) for severe Henoch-Schonlein purpura (HSP) nephritis. METHODS: Twenty patients were evaluated retrospectively. All underwent biopsy before treatment, and 13 underwent biopsy after therapy. We developed a scale based on glomerular, tubulointerstitial (TI), and vascular changes and assigned all specimens acuity, chronicity, and TI scores. The outcomes of 17 patients were compared with those of a historical control group. RESULTS: Chronicity score at initial biopsy increased with increasing delay between onset of renal involvement and first biopsy (rho = 0.55, P =.016) but did not progress after treatment was initiated. Both acuity (rho = 0.57,P =. 016) and TI (rho = 0.69, P =.003) scores correlated with clinical severity at first biopsy. The TI score correlated negatively with serum albumin (rho = -.60, P <.01). Significantly more patients in the study group than in the control group had a favorable outcome (15 [88%] of 17 vs 32 [54%] of 59, P =.011). CONCLUSIONS: Our scale reflects disease activity and highlights the importance of TI changes in severe HSP nephritis. Outcome comparisons indicate that early treatment with prednisone and azathioprine prevents progression of chronic changes and improves outcome.

Adolescent↗

What is GABAergic inhibition? How is it modified in epilepsy?

A deficit of gamma-aminobutyric acid-ergic (GABAergic) inhibition is hypothesized to underlie most forms of epilepsy. Although apparently a straightforward and logical hypothesis to test, the search for a deficit of GABAergic inhibition in epileptic tissue has revealed itself to be as difficult as the quest for the Holy Grail. The investigator faces many obstacles, including the multiplicity of GABAergic inhibitory pathways and the multiplicity of variables that characterize the potency of inhibition within each inhibitory pathway. Perhaps more importantly, there seems to be no consensual definition of GABAergic inhibition. The first goal of this review is to try to clarify the notion of GABAergic inhibition. The second goal is to summarize our current knowledge of the various alterations that occur in the GABAergic pathways in temporal lobe epilepsy. Two important features will emerge: (a) according to the variable used to measure GABAergic inhibition, it may appear increased, decreased, or unchanged; and (b) these modifications are brain area- and inhibitory pathway-specific. The possible functional consequences of these alterations are discussed.

Animals↗

Kawasaki disease complicated by renal artery stenosis.

We report the case of a child who developed severe renovascular hypertension six months after acute Kawasaki disease. The hypertension was well controlled with enalapril, but there was a gradual decrease in function of the affected kidney. The lesion, an ostial stenosis of the right main renal artery, was not amenable to percutaneous balloon angioplasty, so was treated with bypass surgery. Vasculitis is an important cause of renovascular hypertension in children. This case highlights the importance of regular blood pressure monitoring in children with a history of systemic vasculitis.

Angioplasty↗

[Arachnoid cysts of the middle fossa and associated subdural hematoma. Three case reports and review of the literature].

BACKGROUND AND PURPOSE: We report 3 cases of subdural hematoma associated with arachnoid cyst of the middle fossa, and discuss the treatment. METHODS: Three males aged 33, 63 and 68 were treated in our institution. Before this event the cyst was asymptomatic and unknown. Magnetic resonance imaging was the most contributive radiologic exam. Surgical procedure was limited to subdural hematoma evacuation. The internal wall of subdural hematoma was opened in all cases. RESULTS: The clinical outcome was good for all patients. The CT or MRI scan follow-up 3 months later revealed nearly total disappearance of subdural hematoma for 2 out of 3 cases. For one patient the volume of arachnoid cyst decreased. CONCLUSIONS: We propose subdural hematoma drainage without any specific treatment (shunt or fenestration) of the arachnoid cyst, for this category of patient.

Adult↗

Pancreatic secretory response to feeding in the calf: CCK-A receptors, but not CCK-B/gastrin receptors are involved.

In bovine species, as in human, the pancreas predominantly expresses cholecystokinin-B (CCK-B)/gastrin receptors. However, the role of this receptor in the regulation of meal-stimulated pancreatic enzyme release has not been determined. In milk-fed calves, we previously described prandial patterns of exocrine pancreatic secretion and a long prefeeding phase was observed. The present study was aimed at determining both the role of external stimuli in the outset of the prefeeding phase and the implication of pancreatic CCK-A and CCK-B/gastrin receptors in the mediation of pancreatic response to feeding. The first objective was studied by suppressing external stimuli associated with food intake (unexpected meal) and the second by infusing highly specific and potent antagonists of CCK-A (SR 27897) and CCK-B/gastrin (PD 135158) receptors during the prandial period. When calves were given an unexpected meal, the long prefeeding increase in pancreatic secretion was absent. SR 27897 (but not PD 135158) inhibited the preprandial phase and greatly reduced postprandial pancreatic juice and enzyme outflows. The expectancy of a meal seemed to elicit an increased pancreatic response right before a meal and CCK-A receptors may mediate this information via neural pathways. The implication of CCK and CCK-A receptors in mediating the postfeeding pancreatic response was also demonstrated. The participation of CCK-B/gastrin receptors in this regulation was not demonstrated.

Animals↗

[Cochlear implants].

A cochlear implant is a technologically advanced medical device that simulates sound in the cochlea by electrically stimulating the hearing nerve. Cochlear implants are designed to help severely or totally deaf individuals who gain little or no benefit from hearing aids. Hearing aids and assistive listening devices amplify sounds. The sounds produced by even the most sophisticated hearing aids may not offer much benefit to people with a severe-to-profound or profound hearing loss in both ears. A cochlear implant is an electronic device that provides the function of the damaged or absent hair cells by providing electrical stimulation to the remaining nerve fibers. The implant provides useful hearing and improved communication abilities to the implant user.

Adult↗

A para-testicular primitive neuroectodermal tumor in an adult: a case report and literature review.

OBJECTIVE: The authors describe the salient clinical, radiologic and histopathologic features of an extremely rare para-testicular primitive neuroectodermal tumor in a 25 year-old man. INTERVENTION: Excisional biopsy of the tumor en bloc was performed. Adjuvant VAdriaC-based chemotherapy (Vincristine, Doxorubicin, and Cyclophosphamide) was given post-operatively. MAIN OUTCOME MEASURES: Histopathologic examination and immunohistochemical studies were performed on formaldehyde-fixed, paraffin-embedded tumor tissue. RESULTS: Histologic examination showed an undifferentiated small cell tumor. The tumor cells stained positively with MIC-2, a marker specific for primitive neuroectodermal tumors. The patient is 12 months post surgery and has completed adjuvant chemotherapy with no evidence of recurrent disease. CONCLUSIONS: This highly unusual, peripheral primitive neuroectodermal tumor should be considered in the differential diagnosis of undifferentiated small cell neoplasms of the genitourinary system in adults, from the kidney to the testicle. We present a patient with a PNET treated based on a Ewing's family of tumors protocol.

Adult↗