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Biomedical subjects

H Simon

Publications and source records attributed to H Simon.

At least 37 records · Page 2Linked to original sources
PubMed1999

Regulation of eosinophil apoptosis: transduction of survival and death signals.

Since eosinophils are prominent in allergic inflammation, investigators became interested in how these cells accumulate in tissues and their role within the inflammatory cascade. There is increasing evidence from several laboratories that eosinophil numbers are regulated in vivo, not only by eosinophil production in the bone marrow, but also by the amount of eosinophil apoptosis. Moreover, it has been directly demonstrated that eosinophil apoptosis is delayed in allergic inflammatory sites, and that this mechanism contributes to the expansion of these cells in tissue. In this article, we review recent studies that shed light on the intracellular pathways that control eosinophil apoptosis.

Animals↗
PubMed1999

[Fotemustine (Muphoran) in 22 patients with relapses of high-grade cerebral gliomas].

Fotemustine is a third-generation nitrosourea characterized by a phosphoalanine carrier group grafted onto the nitrosourea radical, which gives it a high lipophilicity and a better penetration through the cell membrane. Between September 1988 and December 1997, 22 patients with inoperable or incompletely resected recurrent high-grade gliomas of the brain were treated at the University Hospital in Brest (France). Treatment consisted of three weekly infusions of fotemustine (100 mg/m2 days 1, 8 and 15). If patients responded or were stabilized, fotemustine was continued at the same dose, but every three weeks only. Four patients responded to the treatment (18%), while 6 were stabilized (32%). Main toxicity was haematologic (leucopenia and, above all, thrombocytopenia); treatment was only interrupted in one patient for leucothrombopenia, and there was no toxic death. Medium duration of response and/or stabilisation was 6.5 months, and median survival 9.4 months in responding and/or stabilized patients, while it was only 5.0 months if tumour progressed under chemotherapy (median survival for all patients: 7.5 months). Besides, there was a difference in survival in favour of the young patients (< 50 years-median survival = 11.8 months) in comparison with patients between 50 and 60 years (median survival = 6.8 months; p = 0.0282) or elderly patients (> 60 years-median survival = 5.8 months; p = 0.0634). In our series, we did not found any difference in survival according to the initial performance status of patients before treatment. Therefore, fotemustine seems to represent an interesting well-tolerated treatment possibility in patients with inoperable recurrent malignant gliomas of the brain.

Antineoplastic Agents↗
PubMed1999

Pelosi-type vs. traditional cesarean delivery. A prospective comparison.

OBJECTIVE: To determine the effect of a simplified method of cesarean delivery on postoperative febrile morbidity, operative time, blood loss, total cost and length of hospital stay at Yale New Haven Hospital. STUDY DESIGN: From March 22, 1997, until September 26, 1997, 304 consecutive primary low transverse cesarean deliveries were evaluated at Yale New Haven Hospital. The patient age, duration of ruptured membranes, use of prophylactic antibiotics, operative times, blood loss, major complications, analgesic use, diet advancement, length of hospital stay and total cost of hospitalization were recorded for 275 eligible cases. RESULTS: The Pelosi technique was employed in 101 cases, while 174 were performed with Yale's traditional methods. Both groups were comparable regarding demographic characteristics. Two women in the Pelosi group (1.98%) developed postoperative fevers as compared with 17 (9.77%) in the traditional group (relative risk, 4.93; confidence interval, 1.16, 20.91; P = .05). The mean operating time was 27 minutes in the Pelosi group versus 45 minutes in the traditional group (P = .01). The mean costs were $7,623.55 in the experimental group versus $8,613.28 in the controls (P = .001). No significant differences were seen between the use of prophylactic antibiotics, duration of membrane rupture, analgesic use or hospital stay between the two groups. No serious maternal or fetal outcomes occurred in either group. CONCLUSION: Pelosi-type cesarean delivery resulted in significantly decreased operative time, blood loss and overall cost and improved patient outcome over traditional cesarean section.

Adult↗
PubMed1999

The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.

Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.

Adult↗
PubMed1999

Modular transitional implants to support the interim maxillary overdenture.

It has been reported that for implants to become osseointegrated, they must heal in the absence of functional loads for 4 to 6 months. To address the need for undisturbed healing and patient demand for uninterrupted immediate function and esthetics, the Modular Transitional Implant and Prosthetic System has been developed. This case report describes the use of transitional implants to support a removable maxillary overdenture, including methodology and the advantages and disadvantages of the system. The histomorphometric analysis of one of these transitional implants and its surrounding osseous tissue showed a 45% bone-to-implant interface after 6 months of functional loading. The transitional implant system is a sound and economical method of immediate patient restoration that allows for the protected healing of submerged implants.

Bite Force↗
PubMed1998

Rearrangement reactions in the biosynthesis of molybdopterin--an NMR study with multiply 13C/15N labelled precursors.

The genes moaABC of Escherichia coli were ligated into the expression vector pNCO113. The resulting plasmid was transformed into a moeA mutant of E. coli. From cultures of the recombinant strain, a pteridine designated compound Z could be isolated at 5 mg/liter. Compound Z is a product of precursor Z, a biosynthetic precursor of molybdopterin. Cultures of the recombinant E. coli strain were supplied with [U-(13)C6]glucose, [U-(13)C5]ribulose 5-phosphate, or [7-(15)N,8-(13)C]guanine. The culture medium also contained a large excess of unlabeled glucose. Compound Z as well as nucleosides obtained by hydrolysis of RNA were isolated from the bacterial cultures, and their heavy isotope distribution was investigated by one-dimensional and two-dimensional NMR spectroscopy. The labelling patterns of compound Z show that the carbon atoms of a pentose or pentulose are diverted to the ring atoms C6 and C7 and to the side chain atoms C2', C3' and C4' of compound Z. Carbon atom C1' of compound Z is derived from carbon atom C8 of a guanine derivative. The remodeling of the carbon skeleton of the pentose and purine moieties proceed via intramolecular rearrangement reactions.

Carbon Isotopes↗
PubMed1998

Binding of 2-azaanthraquinone derivatives to DNA and their interference with the activity of DNA topoisomerases in vitro.

We have investigated the binding ability to DNA of compounds belonging to the 2-azaanthraquinone-type structure and have examined the effect on the activity of DNA gyrase as well as on mammalian topoisomerases in vitro. Using different biophysical techniques it was found that one of these ligands, 9-((2-dimethylamino)ethyl)amino)-6-hydroxy-7-methoxy-5, 10-dihydroxybenzo[g]isoquinoline-5,10-dione (TPL-I), is an intercalating DNA binding agent, whereas the parent compound tolypocladin (TPL) and a derivative (TPL-II) showed almost no similar affinity to DNA. CD measurements demonstrated a significant and selective binding tendency of TPL-I to alternating purine/pyrimidine sequences with some preference for poly(dA-dT). poly(dA-dT). Tm values were increased of the ligand complex with the alternating AT-containing duplex polymer. The binding to various DNAs was characterized by CD and visible absorption spectral changes. From the latter, different binding constants of 6.2 x 10(5) and 1.5 x 10(5) M-1 were obtained for poly(dA-dT).poly(dA-dT) and poly(dA). poly(dT), respectively. Sedimentation measurements with supercoiled pBR322 plasmid DNA clearly indicated an intercalative binding mechanism associated with an unwinding angle of about 18 degrees. These results suggest that the intercalative binding of TPL-I is promoted by the 2-(dimethylamino)ethylamino group substituted on carbon 9 of the anthraquinone system. The cytotoxic compound TPL-I, but not TPL or TPL-II, effectively inhibited the DNA supercoiling reaction of DNA gyrase and the activity of mammalian topoisomerases I and II as measured by the relaxation assay. TPL-I affects the cleavage reaction of topoisomerases on a single site located in alternating purine-pyrimidine sequence regions. The inhibitory potency of TPL-I can be ascribed to a blocking of cleavage sites on the DNA substrate, which correlates with the sequence preference of the ligand.

Anthraquinones↗
PubMed1998

Pharmacological stimuli decreasing nucleus accumbens dopamine can act as positive reinforcers but have a low addictive potential.

Opioid peptides, through mu and delta receptors, play an important part in reward. In contrast, the role of kappa receptors is more controversial. We examined the possible positive reinforcing effects of a selective kappa agonist, RU 51599, by studying intravenous self-administration in the rat. The effect of RU 51599 on dopamine release in the nucleus accumbens was also studied, as opioids and dopamine seem to interact in the mediation of reward. The behavioural and dopaminergic effects of RU 51599 were compared with those of the mu agonist heroin. Rats self-administered both RU 51599 (6.5, 20 and 60 microg/inj) and heroin (30 microg/inj) at low ratio requirement. When the ratio requirement, i.e. the number of responses necessary to receive one drug infusion, was increased, self-administration of RU 51599 rapidly extinguished, whereas self-administration of heroin was maintained. Intravenous infusion of RU 51599 (100, 200 and 400 microg) dose-dependently decreased (25, 30 and 40%, respectively) extracellular concentrations of dopamine, as measured by means of microdialysis in freely moving rats. In contrast, heroin increased accumbens dopamine (130% over baseline). These results indicate that kappa receptors, similarly to mu ones, can mediate positive reinforcing effects of opioid peptides. However, the strength of the reinforcement is very low for kappa receptors. This suggests that changes in accumbens dopamine do not correlate with the capacity of a stimulus to induce reward or aversion. In contrast, a parallel seems to exist between an increase in accumbens dopamine and the drive to reach or obtain a positive reinforcer.

Animals↗
PubMed1997

Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus.

Pregnenolone sulfate (PREG S) is synthesized in the nervous system and is a major neurosteroid in the rat brain. Its concentrations were measured in the hippocampus and other brain areas of single adult and aged (22-24 month-old) male Sprague-Dawley rats. Significantly lower levels were found in aged rats, although the values were widely scattered and reached, in about half the animals, the same range as those of young ones. The spatial memory performances of aged rats were investigated in two different spatial memory tasks, the Morris water maze and Y-maze. Performances in both tests were significantly correlated and, accompanied by appropriate controls, likely evaluated genuine memory function. Importantly, individual hippocampal PREG S and distance to reach the platform in the water maze were linked by a significant correlation, i.e., those rats with lower memory deficit had the highest PREG S levels, whereas no relationship was found with the PREG S content in other brain areas (amygdala, prefrontal cortex, parietal cortex, striatum). Moreover, the memory deficit of cognitively impaired aged rats was transiently corrected after either intraperitoneal or bilateral intrahippocampal injection of PREG S. PREG S is both a gamma-aminobutyric acid antagonist and a positive allosteric modulator at the N-methyl-D-aspartate receptor, and may reinforce neurotransmitter system(s) that decline with age. Indeed, intracerebroventricular injection of PREG S was shown to stimulate acetylcholine release in the adult rat hippocampus. In conclusion, it is proposed that the hippocampal content of PREG S plays a physiological role in preserving and/or enhancing cognitive abilities in old animals, possibly via an interaction with central cholinergic systems. Thus, neurosteroids should be further studied in the context of prevention and/or treatment of age-related memory disorders.

Aging↗
PubMed1997

Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress-induced corticosterone secretion.

It is well known that the hypothalamo-pituitary-adrenal (HPA) axis is altered by early environmental experiences, particularly in the perinatal period. This may be one mechanism by which the environment changes the physiology of the animal such that individual differences in adult adaptative capabilities, such as behavioral reactivity and memory performance, are observable. To determine the origin of these behavioral individual differences, we have investigated whether the long-term influence of prenatal and postnatal experiences on emotional and cognitive behaviors in adult rats are correlated with changes in HPA activity. To this end, prenatal stress of rat dams during the last week of gestation and postnatal daily handling of rat pups during the first 3 weeks of life were used as two environmental manipulations. The behavioral reactivity of the adult offspring in response to novelty was evaluated using four different parameters: the number of visits to different arms in a Y-maze, the distance covered in an open field, the time spent in the corners of the open field, and the time spent in the open arms of an elevated plus-maze. Cognitive performance was assessed using a water maze and a two-trial memory test. Adult prenatally stressed rats showed high anxiety-like behavior, expressed as an escape behavior to novelty correlated with high secretion of corticosterone in response to stress, whereas adult handled rats exhibited low anxiety-like behavior, expressed as high exploratory behavior correlated with low secretion of corticosterone in response to stress. On the other hand, neither prenatal stress nor handling changed spatial learning or memory performance. Taken together, these results suggest that individual differences in adult emotional status may be governed by early environmental factors; however, perinatal experiences are not effective in influencing adult memory capacity.

Analysis of Variance↗
PubMed1997

Facilitation of cognitive performance in aged rats by past experience depends on the type of information processing involved: a combined cross-sectional and longitudinal study.

The impact of past history on behavior across the life span is largely unknown. This is why the role of previous experience in subsequent memory performances has been studied in a combined longitudinal (animals repeatedly tested) and cross-sectional (animals tested once at various ages) study, in male Sprague-Dawley rats. Different types of memory (reference and working memory) and/or information processing (route or place learning) were assessed in three different tasks (T-maze, Morris water maze, and eight-arm radial maze). Our results indicate that experience prevents age-related impairments in the learning phase of the T-maze and the Morris water maze, in both middle-aged and old rats. Nonexperienced animals of the same age were found to present age-related memory deficits. However, previous experience did not have any effect on the learning of the radial maze or on the reversal performance. It is suggested that controlled processes (intentional and attentional) are impaired by aging and cannot be improved by training, whereas automated processes appear to benefit from it. These data underline the heterogeneity of cognitive aging and indicate that aging is not inevitably accompanied by a decline in performance.

Aging↗
PubMed1997

Extension of a new two-trial memory task in the rat: influence of environmental context on recognition processes.

A two-trial memory task, based on place or object exploration in a Y-maze, was developed to study recognition processes in young and aged Sprague-Dawley rats (Dellu et al., 1992). This paradigm avoids the use of electric shocks or deprivations that may have nonspecific effects, and the task does not require learning of a rule, i.e., involves essentially working memory. A number of behavioral parameters in several animals could be recorded automatically, thus allowing a detailed analysis of behavior and a simultaneous testing of several animals. We extended this task in order to evaluate the role of contextual information in recognition memory. When the contextual environment during acquisition and retrieval trials was unchanged, place recognition remained intact despite interpolated explorations. When the contextual environment during acquisition and retrieval trials was changed, object recognition was impaired. It was clearly shown that the correct choice between two discrete cues (e.g., small objects) is conditional on more diffuse environmental cues. Thus, it can be hypothesized that at least two kinds of recognition processes can be assessed in animals: an automatic process, based on a discrimination between familiarity and novelty, and a second process, more cognitively based and more effortful. In conclusion, the two-trial task in the Y-maze is sensitive, specific, and fast. It allows the study of both spatial and nonspatial memory, allows the study of different levels (automatic vs controlled) of cognitive processes and their neuroanatomical substrates, and may be profitably employed in aging studies and neuropharmacological research in general.

Animals↗
PubMed1997

DNA binding studies and influence on the activity of DNA topoisomerases of bis-netropsins: different effects of analogs containing cis and trans ethylene linkers.

Binding to DNA and synthetic duplex polymers of two bifunctional netropsins and effects on supercoiled plasmid DNA as well as their inhibitory potency on DNA topoisomerases have been investigated. Characteristic differences were found in the DNA binding properties of the two bis-netropsins containing a cis and trans tether as reflected by CD, thermal melting and sedimentation measurements. CD results indicate, that the bis-netropsins interact with DNA by a two-step binding mode depending on the ligand concentration. The trans bis-netropsin may form stable complexes with different DNA's at high salt concentration, whereas for cis bis-netropsin DNA complexes the second binding step is completely abolished. The variations in the DNA binding ability of trans and cis bis-netropsin show a close relationship to the differences observed in their inhibitory effects on DNA topoisomerases. It appeared that trans bis-netropsin more strongly blocks topoisomerase activity than the cis isomer and represents the most potent inhibitor of DNA gyrase. Differences in the DNA. binding ability of the bis-netropsins and their inhibitory potency on topoisomerase activity are explained in terms of bidentate and monodentate binding mode of the trans and cis isomer, respectively.

Binding, Competitive↗
PubMed1997

Beta-adrenergic stimulation enhances left ventricular diastolic performance in normal subjects.

To determine the effects of beta-adrenergic stimulation on transmitral Doppler echocardiography flow characteristics of left ventricular diastolic filling, we studied 10 healthy volunteers aged 23-31 years (mean age, 26.6 years) during intravenous infusion of isoprenaline in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 min). Saline control infusion was given in the same manner in a crossover and blinded protocol. Compared with the infusion of placebo, stepwise increasing doses of isoprenaline caused a dose-related increase in early and late diastolic filling velocities and velocity-time integrals, a lengthening of the acceleration time, and a shortening of the deceleration and filling time. The chosen method proved highly sensitive, as statistically significant changes were detectable at the lowest dose of 0.1 microgram/min for all variables except velocity-time integral of late filling and deceleration time (> or = 0.2 microgram/min). The effects related to dose in a log-linear fashion except for the lengthening of the acceleration time (early ceiling), the increase of peak early filling velocity (increased steepness at higher doses), and the shortening of the filling time. Inclusion of the associated increases in heart rate and systolic blood pressure and the decrease in diastolic blood pressure blunted all treatment contrasts except for the increase of peak early filling velocity. In addition, the hemodynamics with respect to heart rate and loading conditions were not altered at low dosages of drug (< 0.4 microgram/min). Effects of at least the peak early filling velocity must be interpreted as an active adrenergically mediated myocardial relaxation process. These findings have potentially important clinical implications for this noninvasive, readily available, and convenient technique in clinical pharmacology, stress testing, and possibly therapeutic interventions in diastolic dysfunction in humans.

Adrenergic beta-Agonists↗
PubMed1997

[Split-course concomitant radiochemotherapy plus surgery vs. surgery alone in squamous cell carcinoma of the esophagus. A non-randomized retrospective study of 184 patients].

From April 1989 to October 1995, 184 patients with squamous cell carcinomas of the esophagus were treated either with surgery alone (112 patients) or with preoperative concomitant radiochemotherapy (72 patients) (2 courses of 18.5 Gy in 5 fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) days 1-5 and cisplatinum day 2, separated by a 2-week interval) followed by surgery, and by 4 more courses of chemotherapy alone for good responders. Twenty-seven of these last 72 patients showed histological complete response at surgery (37.5%). There was no statistically significant difference in overall survival between the 2 groups although there were much more T1 patients (small tumors < or = 5 cm in the previous TNM classifications) and less T3 patients (evidence of spread beyond the esophagus) in the surgery alone group, and nevertheless, median survival was better in the combined treatment group (33.6 months versus 21.8 months). However, considering tumor size, there was a statistically significant difference in median survival in favor of the combined treatment group for all T2 patients (> 5 cm without evidence of spread beyond the esophagus in the previous TNM classification) (48.6 months versus 13.8 months), both for T2N0 and T2N1 patients, but also for T1N1 patients (< or = 5 cm with nodal involvement). For the few T3 patients (evidence of spread beyond the esophagus in the previous TNM classification), there was no statistically significant difference between the 2 groups, but the survival curves seemed to show some advantage in favor of the combined treatment group for T3N1 patients. The sex of the patients and the third of the esophagus involved by the tumor did not seem to be of any influence on survival. On the other hand, patients 70-year-old and older showed a poorer survival than other patients. Finally, significantly less patients died with loco-regional recurrences in the preoperatory radiochemotherapy group (32% versus 48%) than in the group treated by surgery alone.

Adult↗