Correlation of fecundability and serum estradiol after danazol treatment in patients with advanced endometriosis

OBJECTIVE: To examine the relationship between pregnancy incidence and the level of serum E2 during danazol therapy. DESIGN: Danazol was given by 200 mg four times daily for 3 months. Serum E2 level was checked after completing the therapy, but before stopping medication. Patients then were advised to conceive at the appropriate time over a 6-month period. SETTING: Reproductive and Endocrine Laboratory of the Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. PATIENTS: Infertile women with invasive endometriosis receiving conservative surgery and danazol treatment. INTERVENTIONS: Serum E2 is checked before medication and at the end of danazol therapy, but before stopping medication. MAIN OUTCOME MEASURES: Whether pregnancy is related to the change of serum E2 caused by danazol therapy. RESULTS: There were 24 pregnancies in 38 patients with invasive endometriosis after treatment. Pregnant patients had significantly lower serum E2 levels as compared with the nonpregnant patients. CONCLUSIONS: After conservative surgery for invasive endometriosis associated with infertility, the therapeutic period of danazol treatment could be shortened to 3 months. Because there is significant correlation of fecundability and serum E2 after danazol medication, serum E2 could be a guideline for predicting pregnancy or for prolonging or changing of treatment after danazol therapy.     

A 68-nucleotide sequence within the 3' noncoding region of simian hemorrhagic fever virus negative-strand RNA binds to four MA104 cell proteins

The 3' noncoding region (NCR) of the negative-strand RNA [3'(-)NCR RNA] of the arterivirus simian hemorrhagic fever virus (SHFV) is 209 nucleotides (nt) in length. Since this 3' region, designated 3'(-)209, is the site of initiation of full-length positive-strand RNA and is the template for the synthesis of the 5' leader sequence, which is found on both full-length and subgenomic mRNAs, it is likely to contain cis-acting signals for RNA synthesis and to interact with cellular and viral proteins to form replication complexes. Gel mobility shift assays showed that cellular proteins in MA104 S100 cytoplasmic extracts formed two complexes with the SHFV 3'(-)209 RNA, and results from competition gel mobility shift assays demonstrated that these interactions were specific. Four proteins with molecular masses of 103, 86, 55, and 36 kDa were detected in UV-induced cross-linking assays, and three of these proteins (103, 55, and 36 kDa) were also detected by Northwestern blotting assays. Identical gel mobility shift and UV-induced cross-linking patterns were obtained with uninfected and SHFV-infected extracts, indicating that the four proteins detected are cellular, not viral, proteins. The binding sites for the four cellular proteins were mapped to the region between nt 117 and 184 (68-nt sequence) from the 3' end of the SHFV negative-strand RNA. This 68-nt sequence was predicted to form two stem-loops, SL4 and SL5. The 3'(-)NCR RNA of another arterivirus, lactate dehydrogenase-elevating virus C (LDV-C), competed with the SHFV 3'(-)209 RNA in competition gel mobility shift assays. UV-induced cross-linking assays showed that four MA104 cellular proteins with the same molecular masses as those that bind to the SHFV 3'(-)209 RNA also bind to the LDV-C 3'(-)NCR RNA and equine arteritis virus 3'(-)NCR RNA. However, each of these viral RNAs also bound to an additional MA104 protein. The binding sites for the MA104 cellular proteins were shown to be located in similar positions in the LDV-C 3'(-)NCR and SHFV 3'(-)209 RNAs. These data suggest that the binding sites for a set of the cellular proteins are conserved in all arterivirus RNAs and that these cell proteins may be utilized as components of viral replication complexes.     

The membrane affinities of the aliphatic amino acid side chains in an alpha-helical context are independent of membrane immersion depth

Understanding, predicting, and designing the binding of peptides and proteins to bilayers require quantifying the intrinsic propensities of individual amino acid residues to bind membranes as a function of structural context and bilayer depth. A host-guest study was performed using the peptide host named helix5 in order to determine the membrane affinities of the aliphatic side chains both in an alpha-helical context and as a function of bilayer depth. Use of the alpha-helical host with a constrained geometry allowed the placement of guest sites at three different depths in bilayers and minimized secondary structural changes due to guest substitutions. Circular dichroism and electron paramagnetic resonance (EPR) were used to characterize the aqueous and bilayer-bound structures of the peptide variants. EPR was also used to measure the bilayer-water partition constants of the peptide variants, and the Delta DeltaGtr values (relative to Gly) of the aliphatic amino acid side chains were subsequently calculated. Surprisingly, the DeltaDeltaGtr values did not significantly vary as a function of the guest site depth in bilayers. In addition, the Delta DeltaGtr values determined in an alpha-helical context are reduced to approximately two-thirds of Delta DeltaGtr values determined in other studies for the bilayer-water and octanol-water partitioning of amino acid side chains in extended and unstructured hosts. Both the relative reduction in Delta DeltaGtr values in the context of an alpha-helical host and the invariance of Delta DeltaGtr values with respect to bilayer depth are consistent with the membrane affinities of the aliphatic residues being largely determined by the classical hydrophobic effect.     

Benign and malignant esophageal strictures: treatment with a polyurethane-covered retrievable expandable metallic stent

PURPOSE: To evaluate the clinical effectiveness of a polyurethane-covered, retrievable, self-expandable metallic stent and hook catheter in the treatment of esophageal strictures. MATERIALS AND METHODS: Stents were constructed of 0.4-mm stainless steel wire in a cylindric zig-zag configuration of six to nine bends. Four to eight stents were connected in tandem by dipping in a polyurethane solution. A nylon loop was hooked inside to each bend of the proximal portion of the stent and strung with a thread. Under fluoroscopic guidance, 22 stents were placed in 16 patients with a malignant stricture and five patients with a benign stricture. The stent was removed with a hook catheter 2 months after placement in patients with a benign stricture and when complications occurred in patients with a malignant stricture. All patients had dysphagia with ingestion of soft foods or liquids. RESULTS: Stent placement was technically successful and well tolerated in 20 patients. In one patient, the stent was misplaced but relocated successfully. After stent placement, all patients were able to ingest solid and/or soft foods without dysphagia. After stent removal, strictures showed improvement but recurred in two patients. CONCLUSION: Use of polyurethane-covered, retrievable expandable stents seems to be a feasible and effective method of treatment of benign and malignant esophageal strictures.