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Biomedical subjects

A Lefebvre

Publications and source records attributed to A Lefebvre.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effect of ACTH suppression on adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA in 4-aminopyrazolopyrimidine-treated rats.

4-Aminopyrazolopyrimidine (4-APP) treatments to rats for 3 days induced 2-fold increase of circulating ACTH and 11-fold increase of adrenal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA compared to NaCl-treated controls. This in vivo model was used to study the effect of the suppression of ACTH secretion on the adrenal HMG-CoA reductase mRNA level. Dexamethasone (Dex) administration to 4-APP-treated rats caused a rapid and parallel decline of the levels of plasma ACTH and adrenal HMG-CoA reductase mRNA to 50% within 2.5 h, whereas the free and esterified cholesterol content was increased 5 and 9.4 times respectively. These changes could be counteracted by the co-administration of ACTH with Dex. Aminoglutethimide (AG) administration to 4-APP-treated rats, which increased the adrenal esterified cholesterol content (7.5 times), decreased the HMG-CoA reductase mRNA level (44%), despite plasma ACTH level remaining elevated. Moreover, the participation of newly synthesized protein(s) in the lowering of adrenal HMG-CoA reductase mRNA level induced by ACTH suppression is suggested by the fact that cycloheximide (Cyclo), when co-administered with AG, completely blocked the decrease of HMG-CoA reductase mRNA level, despite the plasma ACTH level decreasing by 68% and the free and esterified cholesterol content increasing 3.9 and 12.3 times, compared to 4-APP-treated rats. Furthermore, the specificity of these effects was established by the fact that the beta-actin mRNA level was not affected by the administration of either Dex, AG, Cyclo, or AG + Cyclo to 4-APP-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine↗
PubMed1990

The double-stranded RNA associated with the '447' cytoplasmic male sterility in Vicia faba is packaged together with its replicase in cytoplasmic membranous vesicles.

The 447 male sterility trait in Vicia faba is strictly correlated with the presence of well-defined membranous vesicles or 'cytoplasmic spherical bodies' not found in fertile isogenic maintainer plants, and by the occurrence of a discrete high molecular weight double-stranded RNA. We have purified these cytoplasmic membranous vesicles and find that they contain the dsRNA together with an RNA-dependent RNA polymerase whose activity depends upon the presence of Mg2+, requires the four-nucleoside triphosphates and is unaffected by inhibitors of cellular transcriptases, e.g. alpha-amanitin and Actinomycin D. The dsRNA can be labelled in vitro by incubating the cytoplasmic vesicles with radioactive NTPs, and the RNA synthesized in vitro is also in a double-stranded form as judged by its resistance to RNase digestion at high salt and its behaviour upon CF-11 chromatography. Treatment of the vesicles with a non-ionic detergent releases the dsRNA in the form of a complex with the RNA-dependent RNA polymerase. The enzyme can still carry out the specific synthesis of dsRNA in these solubilized complexes. The cytoplasmic vesicles therefore isolate this vertically transmitted, self-replicating dsRNA from the cellular milieu: the possible mode of action and relevance of this novel genetic element to the 447 cytoplasmic male sterility trait are discussed.

Cytoplasm↗
PubMed1990

International labour migration from two Pakistani villages with different forms of agriculture.

"This paper is an analysis of the socio-economic situation of two Punjabi villages [in Pakistan]. It makes an attempt to explain why the villagers of these rural places have to seek work abroad. The first part of the paper deals with the agricultural conditions, the non-agricultural activities available to the villagers, and the budgets of different social categories found in the villages. The second part examines the effects of the process of migration on the young people. It particularly discusses the profile of the migrant, the problems faced by him before his departure, the remittances and their utilization, and the impact of emigration upon women's economic role in the villages and upon the traditional social conflicts. The important conclusion of the paper is that these villagers cannot ensure their social, economic, and cultural reproduction."

Agriculture↗
PubMed1990

[Treatment of anemia in chronic hemodialysis patients with recombinant human erythropoietin: long-term results in 15 patients].

Recombinant human erythropoietin (rHu-EPO) was given during 12 to 20 months in 15 long term haemodialysis anaemic (mean Hb: 6.6 +/- 1 g/dl) patients who required no blood transfusion. Patients over 65, or with severe arterial disease or with uncontrolled hypertension were not included in this trial. Correction of anaemia (mean Hb 12.1 +/- 0.6 g/dl) was achieved in all patients and maintained all along the study. An improved sense of wellbeing and increased exercise tolerance were reported by all patients. Appropriate maintenance dosage of rHu-EPO was 74 +/- 6 U/kg i.v. twice weekly. High dose oral and/or intravenous iron therapy was necessary in the absence of previous marked iron overload. One retinal venous thrombosis was the sole severe side-effect encountered. A slight but significant increase of blood pressure was observed with the need of intensifying previous anti-hypertensive therapy in one patient and of starting one in one another. Fine adjustment of the dry weight was necessary to maintain blood pressure in the normal range. Heparin requirements increased in the majority of patients because of hollow fibre clotting but there was no evidence of decreased efficacy of dialysis. In two patients clotting of arteriovenous fistula was not obviously related to the rHu-EPO treatment.

Adult↗
PubMed1989

Hormonal regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA in the rat adrenal gland.

We studied the effect of ACTH on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme. Reductase activity and reductase mass were enhanced by 22- and 6.2-fold respectively in one series of experiments, whereas in another the levels of reductase activity, reductase mass, and reductase mRNA were increased 6.6-, 3.6- and 2.2-fold respectively, following daily administration of exogenous ACTH for 3 days. Daily injection of 4-aminopyrazolopyrimidine (4-APP) to rats for 3 days increased circulating ACTH level 5.4-fold, whereas adrenal HMG-CoA reductase activity, reductase mass and reductase mRNA levels were greatly increased 36-, 10- and 16-fold, respectively. To counteract the effect of elevated plasma ACTH, dexamethasone acetate (Dex) was administered to 4-APP treated rats. At 3 h post Dex administration, plasma ACTH and corticosteroids levels were effectively decreased by 58 and 59%, respectively. The levels of adrenal HMG-CoA reductase mRNA, reductase activity and reductase mass were also diminished by 38, 31 and 40%, respectively. Our results show that rat adrenal HMG-CoA reductase can respond rapidly to hormonal changes, presumably through variations in circulating ACTH levels.

Adenine↗
PubMed1989

Optimal correction of acidosis changes progression of dialysis osteodystrophy.

To investigate an eventual role of acidosis on hemodialysis osteodystrophy we prospectively studied 21 patients who were dialyzed with different amounts of bicarbonate in the dialysate for 18 months. According to the level of bone formation rate (BFR) on a prestudy bone biopsy, patients were split in two subgroups. Inside these two subgroups patients were randomly allocated to two therapeutics groups: 10 patients (group A) were dialyzed with the conventional amount of bicarbonate (33 +/- 2 mmol/liter) in the dialysate; the rest of the patients (group B, N = 11) had 7 to 15 mmol/liter sodium bicarbonate added to the dialysate to obtain 24 mEq predialysis bicarbonate plasma levels. An effective correction of acidosis was shown in group B by a higher predialysis plasma bicarbonate level (15.6 +/- 1 group A vs. 24.0 +/- 0.6 mEq/liter group B, P less than 0.005), which was reached three months after start of the study. Compared to the prestudy bone biopsy, osteoid and osteoblastic surfaces increased in group A but not in group B on the bone biopsies performed at the end of the study. Parathormone plasma level (iPTH), measured with an antiserum which cross reacts with the 44-68 region of PTH molecule, increased during the study in group A but not in group B. This finding suggested progression of secondary hyperparathyroidism (HPT) only in group A patients. Osteocalcin plasma values increased in both groups during the 18 months of the study. Consequently the two subgroups of patients formed on the basis of BFR level were evaluated separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1989

The enhancing effect of adrenocorticotropin on adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase messenger ribonucleic acid level is inhibited by aminoglutethimide but not by cycloheximide.

3-Hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase activity and reductase mRNA level were determined in adrenals from hamsters treated with ACTH, with or without cycloheximide or aminoglutethimide. Both reductase activity and reductase mRNA level were similarly enhanced by ACTH administration compared to levels in NaCl-treated animals. The administration of cycloheximide with ACTH resulted in a 73% decrease in reductase activity compared to control values, but did not prevent the enhancing effect of ACTH on the reductase mRNA level. Furthermore, the administration of cycloheximide alone diminished HMG-CoA reductase activity, but enhanced by 1.1- to 1.6-fold the reductase mRNA level. Coadministration of aminoglutethimide with ACTH also resulted in a decrease (65%) in reductase activity compared to that in NaCl-treated animals. However, coadministration of aminoglutethimide, in contrast to cycloheximide, with ACTH not only prevented the reductase mRNA level increase produced by ACTH, but also resulted in a 30% decrease in the reductase mRNA level compared to that in controls injected with 0.15 M NaCl. In addition, aminoglutethimide alone resulted in 50% and 54% decreases in reductase mRNA level and reductase activity, respectively. Thus, we have shown that both cycloheximide and aminoglutethimide can prevent the enhancing effect of ACTH on HMG-CoA reductase activity, but their modes of action differ. It is likely that the aminoglutethimide inhibition could be the result of a diminution of specific reductase gene transcription, whereas cycloheximide would result in inhibition of the synthesis of specific proteins, including HMG-CoA reductase. In this respect, since the adrenal free cholesterol content was increased in groups treated with ACTH-aminoglutethimide, we postulate that free cholesterol could be one of the important components involved in the regulation of HMG-CoA reductase gene transcription. As for the ACTH-cycloheximide-treated groups, the adrenal free cholesterol content was also increased, but the effect of ACTH on the reductase mRNA level was not prevented, presumably because this drug blocked the synthesis of a putative sterol regulatory protein that is required to repress HMG-CoA reductase gene transcription.

Adrenal Glands↗
PubMed1988

Cortical v trabecular bone aluminum in dialyzed patients.

Differences among measurement of cortical and trabecular bone aluminum (AI) have been observed. Furthermore, its relationship to bone histology has been variable. In order to clarify these points, we have evaluated measurements of bone AI in relation to the source of AI and bone lesion in 25 hemodialysis patients. All patients were dialyzed in the same unit since commencement of dialysis and treated by the same physician. Age of the patients ranged from 29 to 66 years; mean duration of dialysis was 6.6 +/- 3.5 years. Dialysate water has been treated by reverse osmosis since 1980. Bone biopsy was performed in all patients after double tetracycline labeling. AI was measured biochemically in cortical bone (bCAI) and histochemically in trabecular (TAI) and cortical bone (CAI). Mean serum AI (36 +/- 21 micrograms/L) and bCAI (59 +/- 44 micrograms/g) were increased. There were significant correlations between: cortical AI and (1) serum AI (r = 0.71, p less than 0.001); (2) duration of dialysis with softened water (AI content, 55 +/- 21 micrograms/L, r = 0.65, P less than 0.001) but not with total duration of dialysis; and (3) AI ingested since commencement of dialysis (r = 0.57, P less than 0.01). Trabecular AI was not correlated with any of these parameters. None of cortical AI measurements were correlated with bone formation rates (BFR), osteoblastic surfaces (ObS), and resorption surfaces (RS) determined on trabecular bone. However, trabecular AI was inversely correlated with BFR (P less than 0.01) and ObS (P less than 0.05). Serum parathyroid hormone (PTH) was positively correlated with BFR (P less than 0.001) and RS (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Psychosocial adjustment of 20 patients with Treacher Collins syndrome before and after reconstructive surgery.

Eight males and 12 females (mean age, 12.2 years) with Treacher Collins syndrome were studied longitudinally before and after craniofacial reconstruction. The patients and the parents of the 16 patients who were children were interviewed by a psychosocial team (child psychiatrist, psychologist and social worker) 6 months before and 1, 2, 3 and 4 years after surgery. The patients' facial appearance (Hay's Rating Scale), intellectual ability (Wechsler scales), self-esteem (Piers-Harris Self-Concept Scale for Children) and adaptive functioning (DSM III) were measured. The findings indicate that while their intellectual ability was unchanged, their appearance, self-esteem and adaptive functioning improved, peaking 1 year postoperatively and levelling off at the 2- and 4-year postoperative assessments. The improvement in the patients' facial appearance seems to have a direct, positive influence, creating psychosocial and social benefits for them.

Adaptation, Psychological↗
PubMed1987

Effect of ACTH on cholesterol and steroid synthesis in adrenocortical tissues.

Previous studies have established that under normal conditions, adrenal HMG-CoA reductase activity is higher in hamsters than in rats and humans. The hamster reductase activity follows a diurnal rhythm corresponding to that of plasma ACTH and glucocorticoids [Endocrinology 107 (1980) 215] but not to that of aldosterone. ACTH treatments to hamsters increased reductase activity after a latency of 60 min; this enhancement was prevented by cycloheximide [J. steroid Biochem. 24 (1986) 325]. Immunotitration and immunoblotting studies confirmed that ACTH caused an increase in reductase protein synthesis. In rats, long-term (1-9 days) and short-term (3 h) treatments with ACTH also induced increase in adrenal HMG-CoA reductase activity and reductase protein. In the presence of iodoacetamide and inhibitors of proteolytic enzyme, a main specific band of enzyme was evinced in the area of 102 +/- 6 kDaMr, by Western blotting, for both hamster homogenate and microsomal preparations (Endocrinology, 120 (1987]. Similarly Mr values were found with rat adrenal preparations. The concentration of mRNA, analyzed using the c-DNA pRed-10 coding for the Chinese hamster ovary reductase, was increased in adrenals of hamsters treated with ACTH. The reductase mRNA levels also fluctuated during the day in parallel with those of reductase activity and reductase protein. In conclusion, these results indicate that ACTH and other conditions inducing a change in hamster adrenal HMG-CoA reductase activity provoke parallel changes in reductase mRNA and reductase protein content. ACTH acts on the adrenal reductase of species synthesizing large as well as small quantities of cholesterol, thus indicating the general importance of this hormonal control.

Adrenal Cortex↗
PubMed1987

Adrenocorticotropin and the time of day both influence the amount and activity of 3-hydroxy-3-methylglutaryl coenzyme-A reductase in the hamster adrenal.

We studied the effect of ACTH, alone or in combination with cycloheximide, on hamster adrenal 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase protein content (mass) and activity. Immunoblotting was performed on both homogenate and microsomal preparations, using a rabbit antirat liver reductase antibody and 125I-labeled protein A. A dose-dependent increase in HMG-CoA reductase protein content and activity was produced by ACTH. A time-course study revealed a latency of 60 min, followed by a significant increase at 120 and 180 min, in this response. At 180 min, microsomal reductase activity was significantly increased 4.7-fold, whereas the reductase protein content of microsomes and homogenate preparations was enhanced 4.4- and 3.1-fold, respectively. We calculated that only 40-50% of the reductase protein content was microsomal, indicating that more than one pool of the enzyme is present in adrenals. The coadministration of cycloheximide with ACTH not only prevented the hormonal effect on the protein content and activity of the reductase, but also produced, 180 min posttreatment, 58-69% and 65-86% decreases in reductase protein and activity, respectively. Also, both reductase activity and protein content fluctuated in parallel during the day. In the presence of proteolytic enzyme inhibitors and iodoacetamide, a major band in the area of 102K mol wt was evidenced by immunoblotting. These results indicate that ACTH and other conditions that provoke a change in adrenal HMG-CoA reductase activity also induce, in parallel, a change in the reductase protein content. The basic unit of the reductase has an apparent mol wt of about 102K.

Adrenal Glands↗
PubMed1986

Beauty and the eye of the beholder: social consequences and personal adjustments for facial patients.

Patients' pre- and postoperative self-reports were compared with reports of non-medical observers to investigate whether improved self-esteem is a direct result of increased social acceptance in maxillo- and craniofacial patients. Twenty-two children and adolescents undergoing reconstructive surgery for a variety of facial deformities were asked to rate their physical appearance on the Hay's Scale and fill out the Piers-Harris Self-Concept Scale. Their ratings were compared with scores given by a panel of lay volunteers on random presentation of pre- and postoperative photographs of the same patients. Patients rated their appearance as noticeably improved after surgery, their self-esteem rose significantly and they reported more social adeptness and acceptance at home and school. Raters observed only relatively subtle changes. Apparently, quality of life improved for the postsurgical facial patient because of increased self-esteem and confidence, which free him to overcome social barriers.

Adolescent↗
PubMed1986

Fact and fantasy: psychosocial consequences of facial surgery in 24 Down syndrome children.

Twenty-four children with Down syndrome were evaluated to investigate whether appearance, family functioning and intellectual functioning improved after facial reconstruction. Pre- and postoperatively, families were interviewed by a psychosocial team, the children's intellectual functioning was measured and parents were asked to rate their child's facial appearance on the Hay's Scale and to complete the FACES II, a questionnaire determining family functioning. Parents' ratings were compared with the scores of lay raters who viewed randomly presented pre- and postoperative photographs. Measurements of intelligence and family functioning revealed no postoperative improvement and lay raters considered postoperative appearance as slightly less attractive. However, parents rated their children's appearance as noticeably improved and reported happier personal, family and social lives. Thus, positive psychosocial consequences may largely be the result of parents' satisfaction with surgical results, providing them with hope for the future. Presurgical family assessment to clarify surgical limitations and parental expectations is essential.

Adolescent↗
PubMed1986

A psychiatric profile before and after reconstructive surgery in children with Apert's syndrome.

Twenty-five children with Apert's syndrome, characterised by craniosynostosis and symmetrical syndactyly of hands and feet, were seen by a psychosocial team. The patients ranged in age from 1 month to 15 years. All had undergone synostosis release in the first year of life and were being assessed for craniofacial reconstructive surgery. Psychosocial adjustment was evaluated using a semistructured interview, psychometric testing. Piers-Harris Self-concept Inventory and Hay's Appearance Rating Scale administered by a team consisting of a child psychiatrist, psychologist and social worker, 6 months before surgery and 1, 2 and 4 years after surgery.

Acrocephalosyndactylia↗
PubMed1986

On the control of HMG-CoA reductase, a key regulatory enzyme of adrenal cholesterol synthesis.

In this study we have determined the effect of ACTH on the activity of HMG-CoA reductase in microsomes of hamster adrenals. Cycloheximide was used to study the dependence of the increased enzyme activity by ACTH on de novo protein synthesis. Microsomes were prepared and preincubated with and without NaF and in the presence or absence of phosphorylase phosphatase in order to differentiate between expressed (McNaF) and total (McPP) activity. ACTH induced (after 120 and 180 min) significant increases in HMG-CoA reductase activity with a latent period of 60 min for both McNaF and McPP preparations. Cycloheximide alone decreased the activity of the reductase and the coadministration of cycloheximide + ACTH caused a greater loss of activity. Also, both treatments produced an accumulation of free cholesterol in adrenals suggesting an increased turnover of the reductase by these substances. Preincubation of microsomes at 37 degrees C enhanced per se HMG-CoA reductase activity, but the relative increase produced by ACTH treatments or endogenous ACTH remained essentially the same. In conclusion, under experimental conditions used, the enhancement of HMG-CoA reductase activity produced by ACTH seem to be due to increased enzyme synthesis.

Adrenal Cortex Hormones↗