[Cerebral arterial infarction in young adults and resistance to activated protein C].
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Adult↗
Biomedical subjects
P Giraud
Publications and source records attributed to P Giraud.
Thymus accumulation of I-131 after therapeutic dose for thyroid carcinoma.
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Adult↗
Anemia is associated with lower local-regional control and survival after radiation therapy for head and neck cancer: a prospective study.
PURPOSE: To evaluate the prognostic value of anemia in squamous cell carcinomas in the head and neck treated with curative radiation therapy alone. MATERIALS AND METHODS: In a prospective study, the hemoglobin level was measured prior to radiation therapy in 217 patients (188 [87%] men and 29 [13%] women) with cancer of the oral cavity (n = 61 [28%]), oropharynx (n = 53 [24%]), hypopharynx (n = 21 [10%]), and larynx (n = 82 [38%]). Anemia, defined as hemoglobin level below 13.5 g/dL in men and below 12.0 g/dL in women, was diagnosed in 58 (31%) of the men and five (17%) of the women. Median follow-up was 29 months (range, 2-63 months). RESULTS: The 2-year actuarial probability of local-regional control was 69% (95% confidence interval, 63%, 76%). Multivariate analysis showed the relative risk of failure of local-regional control to increase for stage T3 and T4 tumors (1.8 [95% confidence interval, 1.1, 3.1]), stage N3 nodes (3.6 [95% confidence interval, 1.8, 7.1]), weight loss (2.2 [95% confidence interval, 1.3, 4.0]), and anemia (1.6 [95% confidence interval, 1.0-2.7]). The relative risk of death increased for stage T3 and T4 tumors (2.5 [95% confidence interval, 1.4, 4.3]), N3 nodes (4.0 [95% confidence interval, 1.0, 7.9]), oral cavity tumors (2.0 [95% confidence interval, 1.2, 3.2]), male sex (4.1 [95% confidence interval, 1.3, 13.1]), weight loss (2.2 [95% confidence interval, 1.3, 3.7]), and anemia (1.7 [95% confidence interval, 1.03, 2.7]). CONCLUSION: Moderate anemia appeared to be an independent prognostic factor in squamous cell carcinoma of the head and neck treated with radiation therapy alone.
Actuarial Analysis↗
[Changes of the cutaneous micro-relief in superficial radiation-induced fibrosis: a qualitative study].
Cutaneous radiation-induced fibrosis (RIF) is characterized by a skin retraction or atrophy, toughness to the palpation and often entails functional limitation. Its clinical evaluation remains poorly quantified. The aim of this study was to propose an analytical method to quantify RIF skin surface with the replica technique. In this preliminary study, we report the qualitative and quantitative evaluation of the cutaneous microrelief in 44 healthy controls and in four patients presenting a superficial RIF, 3 to 20 years after radiotherapy for cancer. The microrelief of these RIF presented an abnormal anisotropy with a parallel reorganization of cutaneous valleys in three cases out of four, suggesting a premature radiation-induced ageing of the skin. Each subject being his own control, the relative vertical amplitude of the skin microrelief was +/-15% in control skin. Vertical amplitude was respectively increased by 84% in one inflammatory fibrosis (3 years after RT), decreased by 18% in one evolutive fibrosis (6 years after RT), decreased by 26% in one voluminous stabilized fibrosis (8 years after RT) and decreased by 53% in one atrophic fibrosis (20 years after RT). The present study suggests that the variations of the microrelief parameters could reflect the RIF evolution. This technique requires a validation in a larger series of patients, including patients with telangiectasia.
Adult↗
[Multiple (visceral and neurologic) tumors].
OBJECTIVES: We studied the frequency, histology, epidemiological features and delay between tumours with one localization in the central nervous system. We searched for an association between neurological and visceral neoplasia and tried to establish a guideline when central nervous system tumours appear after a visceral tumour. METHODS: From January 1973 to December 1993, we archived all patients admitted for neurological tumours or who had tumours discovered in our ward. Both neurological and non-neurological and malignant and non-malignant tumours which appeared simultaneously or after a delay were recorded. We retained only patients who had one neurological and one or more visceral tumours (n = 11). Multiple neurological or visceral tumours and phacomatosis were excluded. RESULTS: The association between neurological and visceral tumours is an uncommon but not exceptional finding as multiple tumours were seen in 1% of the cases admitted during the study period with a neurological or a visceral tumour. Meningioma and glioma were the most frequent histological type of central nervous system tumours (10 cases out of 11). Malignant melanoma was particularly frequent among the systemic tumours (3 out of 13 tumours). The classical association between meningioma and malignant breast neoplasia was absent in our study but an association of malignant melanoma and tumours of the central nervous system was found in 3 patients. Age and sex were similar for neurological and visceral tumours. The delay separating the discovery of the two tumours was shorter when the first tumour was a neurological tumour. CONCLUSIONS: These findings demonstrate the frequency of associated neoplasia. We did not find the classical association between breast cancer and meningioma but did find one between malignant melanoma and tumours of the central nervous system. This short study emphasizes the usefulness of having histological proof (when possible) before considering a cerebral tumour as a metastasis of a visceral tumour.
Adult↗
Direct effect of calcitriol on the regulation of parathyroid hormone secretion in a case of pseudo-hypoparathyroidism (a 24-month follow-up study).
The diagnosis of pseudohypoparathyroidism with osteitis fibrosa was made in a 51-year-old woman on the basis of hypocalcaemia, elevated plasma PTH (1-84) and blunted cAMP response to hPTH infusion. Radiologically, widespread signs of hyperparathyroidism were observed and quantitative histomorphometry confirmed the increased bone cellular turnover. Treatment with calcitriol (1,25 dihydroxyvitamin D3) induced a dramatic improvement of bone lesions. During treatment PTH (1-84) normalized with high dosage of calcitriol in spite of low or subnormal levels of serum calcium, and subsequently increased for each reduction of calcitriol dosage despite normal calcium levels. Our observations support a major and direct effect of 1,25 dihydroxyvitamin D3 on the regulation of parathyroid secretion of parathyroids glands.
Biopsy↗
Hyperfractionation in the reirradiation of head and neck cancers. Result of a pilot study.
Between November 1988 and May 1992, 19 patients were enrolled in a pilot study to evaluate feasibility and results of a hyperfractionated reirradiation in the treatment of head and neck recurrences or second primary tumors developed in previously irradiated volume. Patients were divided in two groups according to the initial treatment before reirradiation: group 1 included 14 patients treated with radical surgery and reirradiated because histological evidence of positive margins and/or extra capsular spread of tumor in lymph node metastases; group 2 included five patients treated with three cycles of CDDP-5FU for unresectable tumors and reirradiated because they experienced a complete or good partial (> or = 80%) response after chemotherapy. The reirradiation planned dose was 60 Gy in 5 weeks, with two daily fractions of 1.2 Gy spaced by 6-8 h intervals. Reirradiation was delivered exclusively with photon beams in 17 cases and with a combination of photon and electron beams in two cases. Follow-up ranged from 3 to 45 months with a median of 17 months. Of the 19 patients, 13 received the reirradiation scheduled dose of 60 Gy. For the six remaining patients, the reirradiation doses ranged from 45.6 to 57.6 Gy. All patients experienced an acute mucositis which never led to interruption of treatment. Of the 14 patients of group 1, 10 died 3-41 months after reirradiation (mean: 14 months), three were disease-free 16-37 months after reirradiation and one patient was alive with local progressive disease 39 months after the reirradiation. The overall local control within reirradiated volume was 36% before and 43% after salvage surgery. For all group 1 patients, 12- and 24-month overall survival was 64 and 36%, respectively (mean: 21 months). All patients of group 2 presented a local failure within the reirradiated volume. Three of them died 12, 16 and 25 months after reirradiation, while two of them were alive with progressive disease 25 and 30 months after reirradiation, respectively. The mean survival was 22 months. Overall, 15 late complications were noted: five grade 1, eight grade 2 and two grade 3. There was no lethal complication. Four patients alive in September 1993, and whose initial technical files were available, were enrolled in an additional study to assess the cumulative doses delivered by the two irradiations. Despite disappointing loco-regional control rates, a reirradiation of 60 Gy using a hyperfractionated schedule is feasible in terms of acute and late toxicity.
Adult↗
Contribution of parathyroid hormone-related peptide to the evaluation of hypercalcemia.
Hypercalcemia of malignancy is due either to local osteolysis at the site of bone metastases or to production by the malignancy of parathyroid hormone-related peptide, which shares some of the effects of parathyroid hormone. We used a radioimmunoassay (antiserum specific to the amino-terminus) to measure serum parathyroid hormone-related peptide levels in controls (n = 61), chronic renal failure patients (n = 10), patients with primary hyperparathyroidism (n = 19), cancer patients with (n = 35) or without (n = 57) hypercalcemia and/or bone metastases (n = 53 and n = 39, respectively), and patients with hematologic malignancies (n = 15). We set the upper limit of normal of the parathyroid hormone-related peptide assay at 2.7 pmol/L. The peptide was undetectable in two-thirds of healthy controls. Renal failure did not interfere with the assay. Eighteen of the 19 patients with primary hyperparathyroidism had normal levels. In contrast, 82% of patients with humoral hypercalcemia of malignancy (i.e., without detectable bone metastases) had increased levels; in this subgroup there was a significant inverse correlation between serum levels of the peptide and phosphorus. Elevation of parathyroid hormone-related peptide levels was less common among hypercalcemic patients with metastatic bone disease (38%). Four of the seven hypercalcemic patients with hematologic malignancies had elevated parathyroid hormone-related peptide levels. In our overall study population, serum calcium levels were weakly but significantly correlated with parathyroid hormone-related peptide levels. In conclusion, elevated parathyroid hormone-related peptide in a patient with hypercalcemia suggests a malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Contribution of a new technique of digital enhancement for the control of radiation fields].
To increase geometric treatment accuracy in radiation therapy, we used a novel digitized method and original image processing. The radiographic films that are conventionally used for verifying each beam during the treatment were digitized by a Kodak digital system and then an original image enhancement was applied. For the evaluation of our technique, a clinical trial with two tests was used. The trial involved four readers doing 80 reading. The enhanced films were judged to be of higher quality than the non enhanced films (p = 0.001) and were read more accurately (p < or = 0.001). This automatic enhancement of digitized captured portal images can be easily integrated into the busy routine of a radiotherapy department.
Brain Neoplasms↗
Effects of insulin on the release of neuropeptide Y, [Met5]enkephalin and catecholamines from dog adrenal medulla.
Insulin-induced hypoglycaemia is a well-known stimulating factor for the release of adrenaline from adrenal medulla. The present experiment investigates the co-release of catecholamines and neuropeptides (neuropeptide Y and [Met5]enkephalin) from the adrenal medulla in chloralose-anaesthetized dogs after intravenous administration of insulin (0.3 U/kg). The increases in noradrenaline, adrenaline and [Met5]enkephalin were 29.6-, 23.8-, and 27.9-fold basal values, respectively whereas the neuropeptide Y increase was only 1.6 times the baseline. These results show that adrenal [Met5]enkephalin and catecholamines exhibit the same pattern of co-release which is not the case for adrenal neuropeptide Y.
Adrenal Medulla↗
Insulin-like growth factor-I stimulates c-fos and c-jun transcription in PC12 cells.
We analyzed the effects of insulin-like growth factor-I (IGF-I), a polypeptide growth factor which exerts mitogenic effects via specific membrane receptors. The control of IGF-I on c-fos and c-jun transcription was studied in PC12 cells. Gel mobility shift assays with a labeled AP1 consensus binding sequence (TRE: TGACTCA) showed an increase in specific binding upon trIGF-treatment. Gene transfer studies revealed that the increase in AP1 binding is functional since IGF-I stimulates transcription from a reporter gene containing the minimal TRE linked to the chloramphenicol acetyl transferase (CAT) reporter gene. To further characterize the molecular mechanism by which IGF-I increases AP1 activity, we analysed the transcription regulation of c-fos and c-jun using reporter genes containing the respective promoters or specific regulatory elements. Deletion studies with the c-jun promoter, showed that IGF-I stimulates c-jun transcription via a cis acting element(s) localized within the 132 base pairs prior to the transcription start site; possibly the AP1 like element TGACATCA. Similar studies revealed that c-fos stimulation by IGF-I requires the presence of a regulatory sequence spanning the dyad symmetry element (DSE) and the fos AP1-like sequence (FAP). Further experiments using specific elements linked to the minimal unresponsive c-fos promoter, showed that the DSE is the main target for c-fos induction by IGF-I.
Animals↗
Expression of preproenkephalin A gene and presence of Met-enkephalin in dorsal root ganglia of the adult rat.
The expression of the preproenkephalin A gene was investigated in adult rat dorsal root ganglia (DRG). A radioimmunoassayable Met-enkephalin (ME)-like material was detected in 0.1 M HCl extracts of rat DRG, representing approximately 60 pg of ME equivalents/mg of protein. Chromatographic analyses indicated that the major component of the ME-like material coeluted with authentic ME. In northern blot experiments on total RNA extracted from DRG, a cDNA probe corresponding to the entire coding region of rat preproenkephalin A mRNA yielded a single band of the expected size for this mRNA, i.e., 1.5 kb. Polymerase chain reaction (PCR) experiments were carried out with DRG, striatum, and liver cDNAs using two primers flanking the 1,371-1,771 base region of the preproenkephalin A gene. Thirty PCR cycles performed on both striatum and DRG cDNAs generated a single band of 400 bp, as expected, whereas only trace amounts of this product were detectable using liver cDNAs. Nucleotide sequencing of the PCR product obtained with DRG cDNAs revealed a 100% homology with the 1,371-1,771 sequence of the preproenkephalin A gene. In situ hybridization with a cRNA probe showed that about 3.5% of DRG cells expressed the preproenkephalin A transcript. However, most of these cells probably did not process proenkephalin to enkephalins, as thorough immunohistochemical investigations with anti-ME antibodies allowed the detection of only one in approximately 6,000 cells (in 30 sections of DRG) that exhibited ME-like immunoreactivity. Cells expressing preproenkephalin A mRNA were intermediate-sized neurons, suggesting that primary afferent ME-containing fibers belong to the A category and may participate in a local (spinal) inhibitory control of nociception.
Amino Acid Sequence↗
Leuconostoc, a potential pathogen in bone marrow transplantation.
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Adult↗
Localization of the gene encoding peptidylglycine alpha-amidating monooxygenase (PAM) to human chromosome 5q14-5q21.
Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is a multifunctional protein containing two enzymes that act sequentially to catalyze the alpha-amidation of neuroendocrine peptides. Southern blot analysis of human placental DNA demonstrated that PAM is encoded by a single gene. The chromosomal localization of the PAM gene was established using in situ hybridization. A 2.2-kb human PAM cDNA hybridized to human metaphase chromosomes revealed a significant clustering of silver grains over chromosome 5 bands q14-q21. The gene encoding another enzyme important in the post-translational processing of neuroendocrine precursors, prohormone convertase 1 (PC1), is localized in the same region (5q15-q21).
Blotting, Southern↗
Effects of clonidine, dihydralazine and splanchnic nerve stimulation on the release of neuropeptide Y, MET-enkephalin and catecholamines from dog adrenal medulla.
Various neuropeptides are costored together with catecholamines in the adrenal medulla. The concurrent release (evaluated by adrenal vein plasma levels) of these neuropeptides [neuropeptide Y (NPY), met-enkephaline (ME)] and catecholamines [adrenaline (A) and noradrenaline (NA)] from the adrenal gland was examined in chloralose-anesthetized dogs after intravenous administration of clonidine (10 micrograms/kg) and dihydralazine (1 mg/kg). These results were compared to those obtained after the stimulation of the right splanchnic nerve at 1, 5 and 10 Hz frequencies. The increment in the release of catecholamines and neuropeptides was evaluated for dihydralazine and splanchnic nerve stimulation. Dihydralazine (at its maximal effect) induced a significant preferential increase in catecholamines (expressed as mean (SEM): NA: 17.3 (5.4) fold, A: 13.1 (2.6) fold) and ME (16.0 (7.1) fold) versus basal values. However, the significant increase in NPY-LI was only 2.0 (0.4) times the baseline. Splanchnic nerve stimulation induced a frequency-dependent increase in catecholamines and neuropeptides. When the stimulation frequency was increased from 1 Hz to 5 Hz, NA and A levels increased 17.9 (4.3) and 14.0 (2.2) fold, respectively and ME levels 14.1 (3.0) fold. By contrast, NPY-LI was increased only 2.3 (0.3) fold under the same conditions. Increasing the stimulation frequency from 5 Hz to 10 Hz resulted in similar elevations of NA, ME, and NPY-LI adrenal plasma levels (about 4 times) whereas A only increased twice. Clonidine decreased catecholamine and ME adrenal plasma levels (the maximal percent decrease when compared with control values was about 75%) whereas NPY adrenal plasma levels remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Medulla↗
Glutamate, GABA, glycine and taurine modulate serotonin synthesis and release in rostral and caudal rhombencephalic raphe cells in primary cultures.
Control of serotonin release and synthesis by amino acid neurotransmitters was investigated in rat rostral and caudal rhombencephalic raphe cells in primary cultures respectively. Endogenous amounts of taurine, glycine, GABA and glutamate were measured in both types of cultures. These amino acids were spontaneously released to the incubating medium. Exogenous taurine (10(-4) M) inhibited release and synthesis of newly formed [3H]serotonin [3H]5-HT from [3H]-tryptophan only in rostral raphe cells. Glycine (10(-3) M) decreased [3H]5-HT release in both types of cells, synthesis being diminished only in rostral raphe cells. Glycine inhibitory effect was totally blocked by strychnine (5 x 10(-5) M). GABA (10(-4) M) reduced [3H]5-HT metabolism in rostral as well as caudal raphe cells. This effect was totally antagonized in caudal and partially in rostral raphe cells by bicuculline (5 x 10(-5) M) a GABAA receptor antagonist. Baclofen (5 x 10(-5) M), a GABAB receptor agonist, induced a decrease of 5-HT release in rostral raphe cells. These observations suggest that monoamine release was entirely mediated by GABAA receptors in caudal raphe cells although GABAA and GABAB receptors were involved in control of 5-HT metabolism in rostral raphe cells. L-glutamate (10(-4) M) stimulated 5-HT metabolism in both types of cells, effect totally blocked by PK26124 (10(-6) M). N-methyl-D-aspartate (10(-4) M) enhanced 5-HT metabolism and the induced-effect was antagonized by the selective N-methyl-D-aspartate receptor antagonist D,L-2 amino-5-phosphonovaleric acid. Quisqualate (10(-5) M) stimulated [3H]5-HT release only in caudal raphe cells. This effect was mimicked by (RS)-a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, a quisqualate "ionotropic" receptor agonist, this increase being blocked by 6,7-dinitroquinoxaline 2,3-dione. These observations suggest that the glutamate stimulating-induced effect on serotonin metabolism is entirely mediated by N-methyl-D-aspartate receptor-type in rostral raphe cells and that quisqualate "ionotropic" receptors are also involved in caudal raphe cells. Taken together these results show that [3H]5-HT metabolism is controlled by taurine, glycine, GABA and glutamate in rhombencephalic raphe cells in primary cultures. However, some difference in amino acid receptor-types involved in the control of serotonin metabolism are observed according to the rostral or caudal origin of raphe cells.
Animals↗
Opioid binding sites in jerboa (Jaculus orientalis) brain: a biochemical comparative study in the awake-active and induced hibernating states.
1. Using tritiated ligands [3H]DADLE, [3H]DAGO, [3H]EKC and [3H]Bremazocine, we have demonstrated the presence of delta, mu and kappa sites in brain membranes from jerboa (Jaculus orientalis), a desert rodent and a true hibernator. 2. A comparative study was realized in the case of the induced hibernating state, indicating a reduction of binding capacities during the hibernation state. 3. Using radioimmunoassay, the endogenous pentapeptide methionine-enkephalin (Met-enk) was evaluated in different areas of jerboa brain in comparison with the effect of induced hibernation on the level of Met-enk. 4. A thermodynamic analysis of the effect of temperature on the binding of opioids, indicates that the hibernating and the active state are energetically different. delta G degrees, delta H degrees and delta S degrees were calculated. A break of the Van't Hoff plot was observed in the active state at 15 degrees C, indicating a possible transition state of membranous phospholipids and/or proteins. 5. The role of phospholipids was studied, using the effect of phospholipase A2 and membrane reconstitution. Phospholipids play a key role in the opioid binding.
Animals↗
Dopamine decreases striatal enkephalin turnover and proenkephalin messenger RNA abundance via D2 receptor activation in primary striatal cell cultures.
Dopaminergic regulation of striatal enkephalin biosynthesis and secretion was studied in primary neuronal cultures from fetal rat striatum. To allow pharmacological treatment, striatal primary cell cultures were seeded in chemically defined medium onto extracellular matrix. In these conditions, pharmacological treatment of the striatal neurons on the 10th day in vitro for 48 h with 10(-6) M dopamine induced a 50% decrease in preproenkephalin mRNA level concomitant with a 50% decrease in methionine enkephalin neuronal content. These effects of dopamine were mimicked by the D2 agonist bromocriptine (10(-6) M). The decrease in methionine enkephalin neuronal content induced by dopamine or bromocriptine was reversed by the simultaneous application of sulpiride (10(-6) M), a selective D2 antagonist. Interestingly, the D1 agonist SKF 38393 (10(-6) M) application for 24 or 48 h was found to have no significant effect on methionine enkephalin neuronal content. To ensure dopamine regulation of enkephalin secretion, shorter dopaminergic treatments were performed. Dopamine application (10(-6) M) for 2 h had no significant effect on basal methionine enkephalin secretion but significantly decreased (50%) methionine enkephalin secretion induced by KCl 56 mM. This effect of dopamine on the KCl-induced methionine enkephalin secretion was mimicked by bromocriptine (10(-6) M), reversed by sulpiride (10(-6) M) and unaffected by the D1 antagonist SCH 23390 (10(-6) M) application onto striatal neurons. Our data provide direct evidence for a dopaminergic inhibitory control on enkephalin biosynthesis and secretion from striatal cell cultures, mediated through the dopaminergic D2 receptor activation.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗