Steroid withdrawal in HLA-nonidentical living-related donor transplant recipients.
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Biomedical subjects
Publications and source records attributed to R Mendez.
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We have developed and characterized translationally active cell-free systems from Artemia embryos at different developmental times. The optimized lysates from 16 h-developed embryos incorporated radiolabelled amino acids into polypeptides for up to 120 min. The polypeptides synthesized ranged in Mr from 150,000 to 10,000, suggesting that the endogenous mRNA was capable of directing the synthesis of complete polypeptides. Similar results were obtained by using lysates from early developmental stages; even the cell-free system prepared from 1 h-developed embryos was partially active in protein synthesis. Furthermore, all these lysates were capable of re-initiation, as demonstrated by inhibition of initiation with the inhibitors edeine and 7-methylguanosine 5'-triphosphate. Because we found no endogenous protein-synthetic activity in the corresponding lysates from undeveloped embryos, we have used cell-free translation systems from 0 h- and 16 h-developed Artemia embryos to analyse the mechanisms limiting protein synthesis at very early developmental stages. Undeveloped-embryo lysates supplemented with nuclease-treated reticulocyte lysate were capable of translating endogenous mRNAs to give products with a wide spectrum of Mr values, but lysates of 16 h-developed embryos supplemented in this way were not further stimulated. The nuclease-treated lysate appeared to be unnecessary 5 h after resumption of development. These results suggested that a component(s) limiting translation in the undeveloped-embryo lysate was provided by the nuclease-treated reticulocyte lysate, and that this component(s) no longer limited protein synthesis after development. In view of these results, partially fractionated reticulocyte lysates were tested for restoration of protein-synthetic activity in the undeveloped embryo lysate. A high-salt ribosomal wash devoid of ribosomal subunits, which is considered a crude polypeptide-initiation-factor preparation, also restored translation activity in the undeveloped embryo lysate and made it capable of directing the synthesis of both endogenous mRNAs and exogenous (globin) mRNA.
Over 1000 patients were analyzed in two different time intervals, 1978-1983 and 1984-1989; these corresponded to patient groups not treated with cyclosporine and treated with cyclosporine. Analysis of mismatching showed that there was a significant (P less than 0.05) longterm matching effect in the precyclosporine, era with 0 HLA-DR-mismatched recipients having a 9.5-year half-life compared with a 3-year half-life for the 2 HLA-DR-mismatched transplant recipients. The trend was similar for the cyclosporine-treated groups, but not significant. Risk factors for donor age and race of the recipient (P less than 0.05) were identified in the cyclosporine-treated group. Graft survival in the high-risk patient populations was 70% or better in the 0, 1 HLA-ABDR-mismatched groups as compared with less than 60% graft survival in the high-risk transplant recipients with 2-6 HLA-ABDR mismatches. In the cyclosporine era the HLA-ABDR 0, 1-mismatched patient groups showed a significantly better graft survival than was found in all other categories and at all time intervals analyzed. Matching is a way to ameliorate some of the high risk potential associated with less than optimal donor or recipients.
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A new sulfur-rich and basic polypeptide, designated as gamma-hordothionin, has been isolated from barley endosperm by a semi-preparative purification consisting of extraction with a volatile salt solution followed by high-performance liquid chromatography using a reversed-phase C4 column. The isolated polypeptide was found to be homogeneous by micro-two-dimensional gel electrophoresis in the presence of sodium dodecyl sulfate. The complete primary structure of gamma-hordothionin was determined by automatic degradation of the intact, S-carboxymethylated and S-pyridylethylated gamma-hordothionin and fragments obtained by proteolytic cleavage. gamma-Hordothionin consists of a single polypeptide chain of 47 amino acids with a calculated molecular mass of 5250 Da and contains four disulfide bridges. gamma-Hordothionin inhibits translation in cell-free systems derived from mammalian (rabbit reticulocyte, mouse liver) as well as non-mammalian (Artemia embryo) cells, at several levels. At low concentrations (1-10 microM) the protein seems to affect mainly the polypeptide-chain-initiation process, although it might also act at the elongation level. At higher concentrations (20-80 microM) this inhibitor induces activation of an eukaryotic polypeptide-chain initiation factor 2 alpha-subunit (eIF-2 alpha) kinase in hemin-supplemented reticulocyte lysates, as does hemin deficiency. The presence of the disulfide bridges in gamma-hordothionin appears to be essential for the eIF-2 alpha kinase activation. Based on its similarity at both the structural and functional level with the different genetic variants of thionins (alpha and beta-thionins, from wheat and barley), gamma-hordothionin is a putative member of the thionin family.
Epidurally administered clonidine has been reported to produce postoperative analgesia. To assess the efficacy, safety, and appropriate dose of epidural clonidine for post-cesarean section analgesia, we designed a double-blind, placebo-controlled study. Sixty women were randomly assigned to receive epidural administration of saline bolus followed by 24-h saline infusion, 400-micrograms clonidine bolus followed by 10 micrograms/h clonidine infusion, or 800-micrograms clonidine bolus followed by 20 micrograms/h clonidine infusion. Supplemental analgesia was provided with patient-controlled iv morphine. Compared to saline, both clonidine regimens produced analgesia, as measured by verbal pain scores and supplemental iv morphine use during the first 6 h after bolus injection. Time to first morphine use was similar for both clonidine groups and significantly greater than saline. However, compared to saline, only the 20 micrograms/h clonidine infusion resulted in decreased morphine usage over the entire 24-h period. Compared to saline, both clonidine doses decreased blood pressure. This decrease was greater in the 400-micrograms than in the 800-micrograms clonidine group, but no patient required treatment for hypotension. Clonidine decreased heart rate (one patient required atropine for asymptomatic bradycardia) and produced transient sedation. The 800-micrograms clonidine dose prolonged resolution of local anesthetic-induced motor blockade compared to saline. The results suggest that epidurally administered clonidine provides analgesia, as measured by decreased need for supplemental morphine, after cesarean section, but continuous infusion is required for analgesia of more than 6 h duration.
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In 17 ambulatory patients with severe intermittent dysphagia an endoscopic electrosurgical radial incision of a Schatzki ring was made with a modified straight retractable sphincterotome. The incision was successfully accomplished with immediate relief of dysphagia in all patients. Fourteen patients remain asymptomatic with a mean follow-up of 46 months after the first treatment. Three patients required a second incision and they have been asymptomatic for more than 24 months. There was one mild bleeding episode. Endoscopic electrosurgical incision of the Schatzki ring is an effective therapeutic modality in selected patients.