Ewing's sarcoma of the femur: Prognosis in 69 patients treated by the CESS group

We reviewed the treatment outcome of 69 patients with Ewing's sarcoma of the femur. The patients received chemotherapy according to the CESS 81 (n 14), CESS 86 (n 43), and CESS 91P (n 12) protocols. The 10-year relapse-free survival rates were 36%, 65%, and 65% (p = 0.01). 68 patients received local treatment. The primary tumor was treated by surgery without radiotherapy in 28 patients; 1 developed a local recurrence and 7 metastases. 10 patients received radiotherapy alone; 4 developed metastases and 4 local recurrences and metastases. 30 cases had a combination of surgery and radiotherapy; 7 developed metastases and 1 a local recurrence and metastasis. The survival of patients after radiotherapy alone was worse than that of patients after surgery with/without radiotherapy (p = 0.005). Pathological fractures (n 16) did not influence the prognosis.     

The interaction of parafluorohexahydrosiladiphenidol at muscarinic receptors in vitro

1. The antagonistic actions of parafluorohexahydrosiladiphenidol (pFHHSiD) at muscarinic receptors has been studied in cardiac muscle, smooth muscle and cell culture preparations. In this paper, the classification scheme of Doods et al. (1987) is employed. This scheme is based upon differential affinities of muscarinic antagonists. pFHHSiD exhibited high pA2 values at M3 receptors mediating contractions of guinea-pig ileum and oesophageal muscularis mucosae (7.8 and 8.2 respectively) whereas low values were determined at M2 receptors mediating negative inotropic responses in guinea-pig atria (6.0). Intermediate pA2 values were determined at M1 receptors mediating contractions of the canine femoral and saphenous veins. 2. The pA2 values of pFHHSiD at receptors mediating endothelial-dependent relaxation of rat aortic rings, rabbit jugular vein and canine femoral artery (7.6-7.9) were similar to those determined on the ileum. However, the pA2 values of pFHHSiD at receptors mediating contractions of the guinea-pig trachea (7.1), which has been previously shown to possess M3 receptors, were different from those determined in the ileum. 3. The similarity in pA2 values of pFHHSiD between the M3 receptors in guinea-pig ileum and the receptors mediating endothelial-dependent relaxations provide further evidence for the role of M3 receptors in this vascular response. Taken together, pA2 values for pFHHSiD range from 7.1 to 8.2, depending upon the M3 preparation used. The selectivity of the compound therefore for the M3 versus the M2 muscarinic receptor ranged from 13 to 163 fold.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of Human Mammary Cell Line Proliferation by Membrane Lectin-Mediated Uptake of Ha-ras Antisense Oligodeoxynucleotide

The Ha-ras oncogene promotes cell proliferation. Antisense oligonucleotides complementary to the ras gene sequence encompassing a mutated codon 12 selectively induce a cell proliferation inhibition. However, the concentration required to reach an effective inhibition is high due to the low efficiency of the oligonucleotide crossing through cell membranes, leading to a low concentration in the cytosol and/or the nucleoplasm. In the present paper, we show that anti-ras oligonucleotides linked to a glycosylated carrier, serum albumin bearing mannose 6-phosphate residues, are more efficient than free oligonucleotides or oligonucleotides bound to an unglycosylated carrier at inhibiting proliferation of a human tumor mammary cell line expressing the mutated Ha-ras. Using fluorescein-labeled neoglycoproteins and fluorescein-labeled oligonucleotides bound to neoglycoproteins, flow cytometry and confocal microscopy revealed that (i) these tumor cells express a membrane lectin specific for mannose 6-phosphate-bearing proteins, (ii) the membrane lectin actively mediates the uptake of macromolecules substituted with mannose 6-phosphate, and (iii) the fluorescein-labeled oligonucleotides bound to the neoglycoprotein accumulate in intracellular vesicles. Furthermore, with antisense oligonucleotides carried by the neoglycoproteins, the concentration required to inhibit cell proliferation is lower than that of the carrier-free antisense oligonucleotides.     

Laparoscopic hysterectomy

Summary Thirty-three patients were selected for laparoscopic hysterectomy and operated on in the Department of Obstetrics, Gynecology and Reproductive Medicine of Clermont-Ferrand University Hospital. Surgical techniques included blunt dissection with scissors and bipolar coagulation to achieve hemostasis. A case was considered successful when all the uterine vessels were treated by laparoscopy. Twenty-four cases were completed laparoscopically (72.7%). None of these patients had postoperative bleeding; 22 had an uneventful postoperative recovery. Nine procedures were converted to laparotomy (27.3%), five because of a difficult or unsatisfactory hemostasis. We conclude that in selected cases, a total hysterectomy can be performed safely by experienced laparoscopists. Further technological progress is necessary to make this procedure more acceptable. Its value as compared to the others will have to be demonstrated.     

Nonadrenergic [3H]idazoxan binding sites are physically distinct from alpha 2-adrenergic receptors

We have recently demonstrated that the alpha 2-adrenergic radioligand [3H]idazoxan also labels additional sites that do not recognize catecholamines but bind with high affinity several chemically distinct drugs previously assumed to be highly selective for alpha 2-adrenergic receptors [Mol. Pharmacol. 35:324-330 (1989)]. We now have used three approaches to distinguish the nonadrenergic [3H]idazoxan sites from alpha 2-adrenergic receptors. (a) No nonadrenergic [3H]idazoxan binding sites were found in COS-7 cells transfected with the genes for the two known alpha 2-adrenergic receptor subtypes. (b) The ratio of alpha 2-adrenergic and nonadrenergic [3H]idazoxan sites in human platelet membranes varied considerably between various donors. (c) Highly purified platelet plasma membranes were enriched for alpha 2-adrenergic receptors but did not contain any nonadrenergic [3H]idazoxan binding sites. We conclude that the nonadrenergic [3H]idazoxan binding sites are not co-expressed with alpha 2-adrenergic receptors and at least in human platelets may be located in an intracellular compartment.     

Alcohol effects on the percentage of beta waves in the electroencephalograms of twins

Electroencephalogram (EEG) recordings were made from 26 pairs of monozygotic (MZ) and 26 pairs of dizygotic (DZ) adult male twins, before and after alcohol ingestion. After a baseline EEG and a light breakfast, 1.2 ml/kg of ethanol was given orally over 15 min and the EEG repeated four times at hourly intervals. Alcohol caused a significant drop in the percentage of beta waves (14-30 cycles/sec) during the 1st hr. For the percentage of beta waves in 38 pairs of twins with complete data, MZ twin beta-wave intraclass correlations (RMZ) ranged between 0.85 and 0.91 before and after alcohol, but the DZ intraclass correlations (RDZ) started at 0.54 and fell to 0.05 at 2 hr after alcohol before recovering to baseline levels. These correlations resulted in heritability estimates [2(RMZ-RDZ)] of 0.68 at baseline and 1.73 at 2 hr. A heritability of 1.43 was found for the 1st hr drop in percentage of beta waves (RMZ = 0.78, RDZ = 0.06). These unrealistically high heritabilities, due to RDZ's approaching 0.0, suggest a failure of assumptions in the linear twin model that was used. Also, these findings are similar to, but more exaggerated than, findings in resting EEG's and visually evoked EEG potentials of twins and are compatible with the influence of gene interactions.     

The presence of messenger RNA for HLA class I in human platelets and its capability for protein biosynthesis

Summary. In order to determine whether platelets contain specific messenger RNA encoding for HLA class I molecules, polymerase chain reaction (PCR) was performed with RNA from different platelet donors. Two amplified 300 bp and 279 bp cDNA fragments were obtained which encompassed sequences from 321 to 620 and from 795 to 1073. The 300 bp fragment encodes exon 2 and exon 3, the 279 bp encodes a portion of exon 4, exon 5, exon 6 and a portion of exon 7. A 300 bp nested PCR product from one donor, that encoded for the highly polymorphic region α2, was cloned and sequenced. The resulting nucleotide sequences fitted to the expected sequence for HLA B*3801 of this donor. Sequence analysis of the 279 bp PCR product demonstrated the presence of exon 5 encoding for the 117 bp transmembrane domain.
In addition, de novo protein biosynthesis was studied by radioimmunoprecipitation of HLA class I molecules from ³⁵S-methionine metabolically labelled platelet lysates with a monoclonal antibody (mab) w6/32 specific for a monomorphic epitope on the heavy chain of HLA class I antigens. Analysis of the immunoprecipitates on SDS polyacrylamide gel electrophoresis showed a specific band with apparent molecular weight (M_r) of 44 kD corresponding to integral membrane HLA protein.
On the basis of these results, we conclude that platelets contain specific messenger RNA encoding for HLA class I molecules and have the capability to synthesize the integral HLA membrane protein.     

Pharmacokinetics of prednisolone in children with the nephrotic syndrome

The aim of this study was to establish whether the criteria for the clinical effectiveness of steroids are correlated with the pharmacokinetics of prednisolone in children treated with prednisone during an attack of idiopathic nephrotic syndrome (INS). Thirteen patients with nephrosis were included. Prednisolone, prednisone and cortisol levels were measured using a specific high-performance liquid chromatography assay after an oral dose of 1 mg/kg body weight of prednisone taken at the onset of the disease. All the pharmacokinetic parameters, including the conversion of prednisone to prednisolone were similar to the data already published in children with INS. No correlation was found between the values of pharmacokinetic parameters and criteria of clinical effectiveness. Hypo-albuminaemia was significantly correlated with the area under the plasma-concentration curve but not with the elimination half-life of prednisolone. Moreover, the prednisolone elimination half-life correlated with the urinary exretion of 17-hydroxycorticosteroids achieved in the first 6h. The present study suggests that routine measurements of prednisolone kinetics do not help when assessing the treatment of children with INS.     

Demonstration of extrachromosmal DNA fromBabesia equi merozoites

An extrachromosomal nucleic acid element was detected in high-molecular-weight DNA preparations formBabesia equi merozoites. This extrachromosomal element was shown to be DNA rather than RNA and had an apparent fragment size of about 9 kilobasepairs (kb). Hybridization experiments using purified 9-kb DNA as a probe revealed sequence homologies with extrachromosomal DNA from two otherBabesia species.