Search PubMed⌕ Search

Biomedical subjects

A Levy

Publications and source records attributed to A Levy.

At least 181 records · Page 10Linked to original sources
PubMed1995

Transferable clastogenic activity in plasma from patients with Fanconi anemia.

The present study was conducted on 13 patients with Fanconi anemia. 25 parents and 12 siblings. The chromosomal instability characteristic of this congenital breakage syndrome was associated with the presence of transferable clastogenic material in the plasma, as also reported previously for ataxia telangiectasia and Bloom's syndrome. While all plasma ultrafiltrates from homozygotes had chromosome damaging properties, the clastogenic material had to be concentrated in most heterozygotes to reach detectable levels. The clastogenic effect was exerted via the intermediacy of superoxide radicals, since it was regularly inhibited by superoxide dismutase (SOD). This adds further evidence for a prooxidant state in this hereditary disease. The autosustained clastogenic activity possibly plays a role in the progressive impairment of blood cell-producing bone marrow and may predispose patients to develop cancer and leukemia. Prophylactic use of antioxidants may be recommended, using clastogenic plasma activity as a guide.

Adolescent↗
PubMed1995

Cloacal exstrophy sequence: an exceptional ultrasound diagnosis.

OBJECTIVE: To establish sonographic criteria for an early prenatal diagnosis of cloacal exstrophy sequence, an extremely rare congenital malformation. METHODS: We assessed all cases of anterior midline abdominal wall defects occurring between November 1, 1986, and May 31, 1993. The charts of those with cloacal exstrophy sequence were reviewed thoroughly. The sonographic findings in each case of cloacal exstrophy sequence were evaluated and compared with the ultrasonic manifestations in other types of anterior abdominal wall defects. RESULTS: During the study period, six cases of cloacal exstrophy were diagnosed by ultrasound and confirmed by postnatal autopsy examination. Two of the cases were in different twin gestations. There were 58,288 deliveries during the study period; 665 (1.14%) major malformations were diagnosed ultrasonographically. Identical specific sonographic signs appeared in all six cases of cloacal exstrophy. These included a large infraumbilical, anterior midline defect, a protruding large omphalocele, an absent bladder, a narrowed thorax, a distorted spine, a large sacral meningomyelocele, and bilateral clubfeet. In all cases, the fetal bowel was floating in a large amount of ascites within the omphalocele sac. Polyhydramnios was present in four of the six cases. CONCLUSION: Based on our sonographic criteria, we believe that an accurate prenatal diagnosis of cloacal exstrophy sequence is feasible, even in the first trimester of pregnancy. These signs distinguish cloacal exstrophy from other types of midline anterior abdominal wall defects, ie, gastroschisis, amniotic band syndrome, and limb-body wall complex (body-stalk syndrome).

Adult↗
PubMed1995

Water deprivation in the rat induces nitric oxide synthase (NOS) gene expression in the hypothalamic paraventricular and supraoptic nuclei.

We examined the effects of water deprivation on nitric oxide synthase (NOS) gene expression in the rat hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), using in situ hybridization histochemistry. Dehydration caused a significant increase in NOS gene transcripts in the PVN and SON but not in the subfornical organ (SFO). The results suggest that dehydration has a major effect on the NOS gene expression in the PVN and SON.

Animals↗
PubMed1995

Radiation-induced clastogenic factors: anticlastogenic effect of Ginkgo biloba extract.

Clastogenic factors (CFs) were first described in the blood of persons irradiated accidentally or for therapeutic reasons. Work of our laboratory has shown that they occur also under other circumstances, which are characterized by oxidative stress, and that CF-induced chromosome damage is regularly prevented by superoxide dismutase (SOD). Recently we found CFs in a high percentage of salvage personnel of the Chernobyl reactor accident. These liquidators represent a high-risk population and might benefit from cancer chemoprevention by antioxidants. SOD would have to be injected and is not appropriate for long-term prophylactic treatment. In the present study, we therefore evaluated the anticlastogenic effect of the Ginkgo biloba extract EGb 761, which is known for its superoxide scavenging properties. EGb 761 was tested on CF-treated blood cultures of healthy donors. After establishing the optimal protective EGb concentration, using CFs produced by irradiation of whole blood from healthy volunteers, the extract was tested on cultures exposed to CFs from plasma of persons irradiated as liquidators. The anticlastogenic effect could be confirmed for a final concentration of 100 micrograms/ml. In 12 consecutive experiments, CFs induced an average of 18.00 +/- 4.41 aberrations/100 cells. This was reduced to 7.33 +/- 3.08 in the parallel cultures receiving 100 micrograms/ml EGb 761 (p < .001). SOD was anticlastogenic in the same system at concentrations of 30 cytochrome C units/ml (approximately 10 micrograms/ml). Preliminary results obtained in a small series of liquidators showed regression or complete disappearance of CFs in the plasma after 2 months of treatment with EGb 761 (3 x 40 mg/d).

Antimutagenic Agents↗
PubMed1995

Plasma from patients exposed to ischemia reperfusion contains clastogenic factors and stimulates the chemiluminescence response of normal leukocytes.

Clastogenic factors (CFs) are released by cells exposed to superoxide radicals and are found in various situations of oxidative stress. Certain of their components stimulate further superoxide production by competent cells, as shown with cytochrome c assay in previous work. In the present study, we report CF formation after ischemia reperfusion in patients undergoing coronary bypass surgery. Plasma ultrafiltrates, collected 20 min after reperfusion, had clastogenic properties in contrast to those collected before ischemia. We also show that the luminol-enhanced chemiluminescence response of neutrophils from healthy persons is increased when these cells are exposed to CF-containing postreperfusion samples from patients. Light emission was reduced to control values in the presence of superoxide dismutase. The burst of oxyradicals upon reperfusion is probably the initiating event of CF formation, which in turn leads to further oxyradical generation. This amplification process may explain why detectable levels of CF need a delay of at least 10 min. The activated state of neutrophils in ischemia reperfusion is at once a consequence and a source of CFs. Individual variation in the persistence of this clastogenic and leukocyte-activating material was observed. Therefore, antioxidants for prevention of ischemia reperfusion injury should be continued during the postoperative course.

Antioxidants↗
PubMed1995

Clastogenic factors in plasma of HIV-1 infected patients.

The objective of this study was to investigate the clastogenic activity of plasma ultrafiltrates from HIV-1 infected patients. Clastogenic factors are chromosome-damaging agents with low molecular weight (< 10,000 daltons) which cause chromosome aberrations, sister chromatid exchanges, DNA strand breakage, and gene mutation. They have first been described in the plasma of irradiated persons, but they are also found in hereditary breakage syndromes and chronic inflammatory diseases with autoimmune reactions. Their formation and their clastogenic effects are modulated by superoxide anion radicals. We analyzed a total of 22 HIV-1 positive patients in comparison to 20 reference plasma samples from healthy HIV negative blood donors of similar age. The plasma ultrafiltrates (filter cutoff 10,000 daltons) from patients induced a statistically significant increase in chromosomal breakage in the cytogenetic test system (20.5 +/- 6.8 aberrations per 100 cells), while no increase was observed in test cultures exposed to plasma ultrafiltrates from healthy blood donors (6.3 +/- 2.9 aberrations per 100 cells). The breakage values were slightly, but not significantly, lower in the 10 patients with more than 200 T-helper cells/ml (18 +/- 4 aberrations per 100 cells), than in the 12 patients with less than 200 T-helper cells/ml (22.3 +/- 7.9 aberrations per 100 cells). HIV patients with high clastogenic activity (induction of more than 20 aberrations per 100 cells, range 20 to 39) showed higher plasma levels for malondialdehyde than those with lower clastogenic activity (less than 20 aberrations per 100 cells, range 12 to 18). However, the difference was statistically not significant. Another lipid peroxidation product, 4-hydroxynonenal, was increased equally in both groups. There were no significant differences in water- and lipid-soluble plasma antioxidants between the low- and high-breakage group. In agreement with previous findings, the clastogenic effects of plasma ultrafiltrates in the test cultures were reduced by the antioxidant enzyme superoxide dismutase. The presence of clastogenic factors in the plasma of HIV patients is further evidence for a prooxidant state in these persons. Since clastogenic factor formation appears to occur at an early stage of the disease, it may be significant for virus release or activation, because of the superoxide anion stimulating effects of clastogenic factors. From a practical standpoint, clastogenic factors may be useful for evaluation of promising drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Human COL2A1-directed SV40 T antigen expression in transgenic and chimeric mice results in abnormal skeletal development.

The ability of SV40 T antigen to cause abnormalities in cartilage development in transgenic mice and chimeras has been tested. The cis-regulatory elements of the COL2A1 gene were used to target expression of SV40 T antigen to differentiating chondrocytes in transgenic mice and chimeras derived from embryonal stem (ES) cells bearing the same transgene. The major phenotypic consequences of transgenic (pAL21) expression are malformed skeleton, disproportionate dwarfism, and perinatal/neonatal death. Expression of T antigen was tissue specific and in the main characteristic of the mouse alpha 1(II) collagen gene. Chondrocyte densities and levels of alpha 1(II) collagen mRNAs were reduced in the transgenic mice. Islands of cells which express cartilage characteristic genes such as type IIB procollagen, long form alpha 1(IX) collagen, alpha 2(XI) collagen, and aggrecan were found in the articular and growth cartilages of pAL21 chimeric fetuses and neonates. But these cells, which were expressing T antigen, were not properly organized into columns of proliferating chondrocytes. Levels of alpha 1(II) collagen mRNA were reduced in these chondrocytes. In addition, these cells did not express type X collagen, a marker for hypertrophic chondrocytes. The skeletal abnormality in pAL21 mice may therefore be due to a retardation of chondrocyte maturation or an impaired ability of chondrocytes to complete terminal differentiation and an associated paucity of some cartilage matrix components.

Animals↗
PubMed1995

Returning home after acute hospitalization in two French teaching hospitals: predictive value of patients' and relatives' wishes.

Identifying elderly patients who are unable to return home immediately after acute hospitalization is difficult. For these patients, early planning of discharge might reduce the length of hospitalization. We conducted a cohort study to investigate the roles of patients' characteristics and patients' and principal carers' wishes about patients returning home in predicting the outcome of hospitalization for 510 patients aged 75 years or more admitted to acute medical care units via the emergency departments of two teaching hospitals in Paris (France). Patients' characteristics and patients' and principal carers' wishes were investigated within 24-48 hours of admission. The outcome of hospitalization was defined as discharge to home or residential/nursing home. The opposition of the principal carer to a patient returning home was the most powerful predictor of discharge to a residential/nursing home. Advanced age, living alone, disability in Activities of Daily Living, altered mental state and presence of a chronic condition fatal within 4 years were also independently associated with discharge to a residential/nursing home. The patient's wishes were predictive in univariate but not in multivariate analysis. These results suggest that the principal carer's wishes about a patient returning home might be taken into consideration early in a hospital stay for more effective discharge planning.

Activities of Daily Living↗
PubMed1995

Nucleotides as extracellular signalling molecules.

There is now wide acceptance that ATP and other nucleotides are ubiquitous extracellular chemical messengers. ATP and diadenosine polyphosphates can be released from synaptosomes. They act on a large and diverse family of P2 purinoceptors, four of which have been cloned. This receptor family can be divided into two distinct classes: ligand-gated ion channels for P2X receptors and G protein-coupled receptors for P2Y, P2U, P2T and P2D receptors. The P2Y, P2U and P2D receptors have a fairly wide tissue distribution, while the P2X receptor is mainly found in neurons and muscles and the P2T and P2Z receptors confined to platelets and immune cells, respectively. Inositol phosphate and calcium signalling appear to be the predominant mechanisms for transducing the G-protein linked P2 receptor signals. Multiple P2 receptors are expressed by neurons and glia in the CNS and also in neuroendocrine cells. ATP and other nucleotides may therefore have important roles not only as a neurotransmitter but also as a neuroendocrine regulatory messenger.

Amino Acid Sequence↗
PubMed1995

Inhibition of hypothalamic nitric oxide synthase gene expression in the rat paraventricular nucleus by food deprivation is independent of serotonin depletion.

We have investigated the effects of food deprivation on nitric oxide synthase (NOS) transcript levels in the rat paraventricular (PVN) and supraoptic nuclei (SON), using in situ hybridization histochemistry. Food deprivation for 48 h significantly and consistently reduced NOS transcript prevalence by approximately 50% in both sites. Since there is considerable evidence for an important role of 5-HT in feeding behaviour, we then examined the effect of food deprivation on NOS gene expression in the PVN following para-chlorophenylalanine (PCPA)-induced hypothalamic 5-HT depletion. As starvation causes central down-regulation of the thyroid axis, changes in thyrotropin-releasing hormone (TRH) and pituitary thyrotrophin (TSH) transcript prevalence were used as internal controls. PCPA pretreatment (200 mg/kg body weight as a single daily dose ip for 2 days) had no significant effect on basal levels of NOS, TRH or TSH transcripts, or on the effect of a subsequent 48 h fast, which significantly reduced all three. These results show for the first time, that food deprivation for 48 h significantly reduces NOS gene expression in the rat PVN and SON. Secondly, that basal levels and the fasting-induced reductions in the prevalence of NOS, TRH and TSH transcripts were not affected by PCPA-induced hypothalamic 5-HT depletion. Therefore, at least under the experimental conditions used here, 5-HT does not appear to be involved in setting baseline levels- or in the starvation-induced inhibition of NOS or thyroid axis gene expression in the PVN.

Animals↗
PubMed1995

Influence of environmental colour and diurnal phase on MCH gene expression in the trout.

Melanin-concentrating hormone (MCH) gene expression in the brain of rainbow trout, reared and maintained in either pale or black-coloured tanks, was studied using in situ hybridization histochemistry. MCH transcripts were most prevalent in the magnocellular neurones of the nucleus lateralis tuberis (NLT), which project to the pituitary gland. They were also present, although at much lower levels, in dorsally projecting parvocellular neurones, sited more posteriorly above the lateral ventricular recess (LVR). In the NLT the most intense hybridization signal was seen over the pituitary stalk; above the LVR, the most active neurones were located caudally. In both the NLT and above the LVR, MCH hybridization signal was 4-fold stronger in white-reared fish than in black-reared fish. There was also a marked diurnal variation in MCH expression in both sites, with high levels at 16.00 h and lower levels at 04.00 h. The results show that gene activity in both hormonal (NLT) and neuromodulator/neurotransmitter (LVR) MCH neurones is induced by pale environmental colour and that MCH gene activity is subject to pronounced diurnal variation.

Animals↗
PubMed1995

S-100 antigen-positive folliculostellate cells are not the source of IL-6 gene expression in human pituitary adenomas.

We have investigated the expression of IL-6 in a random selection of 27 human pituitary adenomas, comprising 8 somatotroph, 5 corticotroph, 3 mammotroph and 11 endocrinologically inactive adenomas, using a 35S-labelled 1.1kb riboprobe complementary to human IL-6. Positive and negative IL-6 transcript controls were generated from the IL-6-secreting human bladder carcinoma cell line T24/83. Tissue from a malignant melanoma was used as a positive S-100 immunocytochemical control tissue. Of the 27 human pituitary adenomas examined by in situ hybridization, 7 (26%) contained IL-6 transcripts: these were 3 of 5 corticotroph adenomas, 2 of 8 somatotrophinomas and 2 of 11 endocrinologically inactive adenomas. In each case, IL-6 transcript-positive cells constituted less than 1% of the total pituitary tissue mass examined. Alternate wax embedded 3 microns thick sections from 5 of the 7 IL-6 transcript positive tumours were examined immunocytochemically for S-100 antigen, or by in situ hybridization for IL-6 transcripts. Immunocytochemistry for S-100 antigen was completely negative in 3 of the 5 tumours and in the remaining 2, there was no evidence of IL-6 transcripts and S-100 antigen co-localization in any of the sections examined. This suggests that in pituitary adenomas, cells other than classical folliculostellate cells are responsible for IL-6 production.

Adenoma↗
PubMed1995

Cloning and expression of melanin-concentrating hormone genes in the rainbow trout brain.

Salmonids, a group of tetraploid fish including salmon and trout, produce the vertebrate neuropeptide melanin-concentrating hormone (MCH) in a group of hypothalamic magnocellular neurons in the nucleus lateralis tuberis (NLT). NLT neurons project both to the brain and to the neural lobe of the pituitary gland from where MCH is released into the circulation to play a central role in camouflage (+/- stress). We have cloned and sequenced the MCH1 and MCH2 genes from the rainbow trout, Oncorhynchus mykiss, and used the data firstly to examine the position of O. mykiss in salmonid phylogeny, and secondly to enable central nervous system MCH1 and MCH2 gene expression to be mapped. In the immature adult female trout brain, only MCH2 was detectable at the hybridization stringency used. In addition to the known location of MCH-positive neurons, immunocytochemistry and in situ hybridization histochemistry revealed a previously undescribed nucleus of MCH-positive neurons located more dorsal and posterior to those of the NLT, over the paraventricular organ of the lateral ventricular recess. Axons from this second group of MCH neurons project dorsally into the brain, while a few extend down toward the lateral ventricle near the paraventricular organ. They make little, if any, direct contact with the neurohypophysis, and thus may subserve a central function, unrelated to hormonal colour regulation.

Amino Acid Sequence↗
PubMed1995

Hypothalamic nitric oxide synthase gene expression is regulated by thyroid hormones.

We investigated the effects of thyroid status on nitric oxide synthase (NOS) gene expression in the rat hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). Propylthiouracil (PTU)-induced hypothyroidism in male rats produced a highly significant reduction in NOS gene transcripts in the PVN and SON, as assessed by quantitative in situ hybridization histochemistry with a specific oligodeoxynucleotide probe. The addition of T3 (40 micrograms/kg) to the PTU-containing diet completely prevented the reduction in NOS transcripts. Hyperthyroidism, induced by adding 160 micrograms/kg T3 to the food, more than doubled the prevalence of NOS transcripts in the PVN and SON after a similar time. Up-regulation of NOS gene transcripts induced by the osmotic stimulus of chronic salt loading was markedly attenuated by PTU-induced hypothyroidism. These results demonstrate a major effect of thyroid status on regulation of NOS gene expression in the hypothalamus.

Amino Acid Oxidoreductases↗
PubMed1995

Hypothalamic GH receptor gene expression in the rat: effects of altered GH status.

GH synthesis and release from the anterior pituitary is governed by the opposing actions of somatostatin (SS) and GH-releasing factor (GRF), derived from the periventricular and arcuate nucleus (ARC) of the hypothalamus respectively. GH is known to regulate its own release by hypothalamic autofeedback mechanisms, but the extent to which this is a direct effect rather than indirectly via the generation of IGFs is still a subject of debate. GH receptors are known to be present in the hypothalamus, but their physiological regulation is poorly understood. We therefore used in situ hybridization histochemistry to investigate the effects of GH status on hypothalamic GH receptor gene expression, using hypophysectomized normal and dw/dw dwarf rats as models of acquired and congenital GH deficiency. Hypophysectomy resulted in a time-dependent reduction in GH receptor gene expression. ARC GH receptor transcripts in untreated dw/dw dwarf rats were half those found in normal animals of the same background strain (16.8 +/- 1.7 vs 9.3 +/- 1.9 d.p.m./mg, P < 0.05). Increasing circulating GH by peripheral infusion of 200 micrograms human GH (hGH)/day for 6 days increased ARC GH receptor expression in dw/dw rats to normal. In contrast, central infusions of hGH at 26.4 and 79.2 micrograms/day for 6 days in normal rats lowered ARC GH receptor gene expression. The sensitivity of GH receptor gene expression within the central nervous system to peripheral and central GH levels suggests that feedback regulation of GRF and/or SS may be mediated directly by these receptors, and that the sensitivity to GH feedback is also subject to autoregulation by GH altering its own receptor expression.

Animals↗
PubMed1995

A computer tomographic classification system for the displaced intraarticular fracture of the os calcis.

The treatment of the displaced intraarticular fracture of the os calcis continues to be controversial. One of the reasons for this is the lack of a workable classification system which would allow comparison among different treatment modalities. Plain radiographs are unable to depict the complex three-dimensional pathology of this fracture. Computed tomography (CT) scanning, however, has the potential to quite accurately depict all components of this injury. At our hospital, a five-part, CT-based classification system has been utilized. This system suggests which fractures will do well with conservative care, and which fractures are amenable to operative stabilization.

Ankle Injuries↗
PubMed1995

Clastogenic factors in the plasma of Chernobyl accident recovery workers: anticlastogenic effect of Ginkgo biloba extract.

Clastogenic factors are found in the plasma of persons irradiated accidentally or therapeutically. They persisted in the plasma of A-bomb survivors over 30 years. Clastogenic factors were found in 33 of 47 Chernobyl accident recovery workers (often referred to as liquidators) in a previous study (I. Emerit et al., J. Cancer Res. Clin. Oncol. 120, 558-561, 1994). In the present study, we show that there is a positive correlation between clastogenic activity and dose and that these biomarkers of oxidative stress can be influenced successfully by appropriate antioxidant treatment. With the authorization of the Armenian Ministry of Health, 30 workers were treated with antioxidants from Ginkgo biloba leaves. The extract EGb 761 containing flavonoids and terpenoids was given at a daily dose of 3 x 40 mg (Tanakan, IPSEN, France) during 2 months. The clastogenic activity of the plasma was reduced to control levels on the first day after the end of the treatment. A 1-year follow-up showed that the benefit of the treatment persisted for at least 7 months. One-third of the workers again had clastogenic factors after 1 year, demonstrating that the process which produced clastogenic factors continued. However, the observation that antioxidants do not have to be given continuously is encouraging for intervention trials on a large-scale basis. These appear justified, since clastogenic factors are thought to be risk factors for the development of late effects of irradiation.

Adult↗