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Duplication of 16p from insertion of 16p into 16q with subsequent duplication due to crossing over within the inserted segment.

Two members of a large family had a similar multiple congenital anomalies mental retardation (MCA/MR) syndrome and an identical aberration of chromosome 16. Their mothers, who are first cousins, had a different abnormality of one chromosome 16, which appeared to be an acrocentric. We interpret these findings as an insertion of a segment of 16p into 16q. following a three-break rearrangement and meiotic crossing over. The two abnormal children have a duplication of 16p11 leads to p13. The clinical manifestations of these patients differ from those of previously reported cases of dup(16p).

Abnormalities, Multiple↗

Patient package inserts. II. Toward a rational patient package insert.

Analysis of the response to a questionnaire on various aspects of drug information showed several significant trends. The importance of the physician as an information source varied directly with age and inversely with educational level of patients. The doctor's importance as a source of information was also greater for those who visited physicians' offices or clinics more and if they were on long-term treatment. Younger persons, those with higher levels of education, and those who were not in regular contact with a physician placed greater importance on non-physician sources. Persons consulting physicians regularly desired less information and knew less about drugs than those who did not regularly see a physician. These findings suggest that the educational role of the physician could be improved and should be directed particularly at the low-income, older patient. In the design of the package insert, particular attention should be given to self-prescribed medications where no other information sources will be operating.

Adult↗

Insertion of hydrophilic amino acid residues in the signal peptide/membrane anchor domain of neprilysin (neutral endopeptidase-24.11) results in its cleavage: role of the position of insertion.

We have expressed in COS-1 cells mutants of neprilysin (neutral endopeptidase-24.11; NEP) in which the hydrophilic sequence S-Q-N-S was either substituted for V42-T-M-I or inserted after T38 in the signal peptide/membrane anchor (SA) domain. These mutations were introduced in full-length NEP (mutants NEP(H1) and NEP(H2), respectively) and a form of NEP lacking its cytosolic tail (mutants NEP delta cyto(H1) and NEP delta cyto(H2), respectively). Immunoblotting showed that NEP(H1) was membrane-bound while NEP delta cyto(H1), NEP(H2), and NEP delta cyto(H2) were secreted. Furthermore, carbonate treatment of isolated intracellular membranes suggested that cleavage of the SA domain was performed in the endoplasmic reticulum, presumably by signal peptidase. Sequencing of the secreted proteins indicated that cleavage of the SA domain mostly occurred at the carboxy side of Ala46 but also at the carboxy side of Ala41 in NEP(H2) and NEP delta cyto(H2). We conclude that the position of the S-Q-N-S sequence influences the accessibility of the cleavage site and, in the case of NEP(H1) and NEP(H2), the efficiency of cleavage of the SA domain.

Amino Acid Sequence↗

Combined endoscopic and percutaneous stent insertion to overcome a problem of percutaneous stent insertion.

Non-operative stent insertion is a well-accepted means of palliating malignant biliary obstruction. The endoscopic approach is often considered the procedure of choice, with the percutaneous technique reserved for endoscopy failures. We recently encountered a patient in whom both techniques proved unsuccessful initially, and in whom palliation was finally achieved by means of a combined endoscopic and percutaneous transhepatic procedure.

Aged↗

A biomechanical comparison of the antegrade inserted universal femoral nail with the retrograde inserted universal tibial nail for use in femoral shaft fractures.

Femoral shaft fractures with and without bony contact were simulated in cadaver specimens fixed with one of two different types of intramedullary locked nail systems; conventional antegrade nail fixation of the femur with the universal AO femoral nail or retrograde insertion in the femur with the universal tibial nail (a smaller diameter slotted nail) were utilized. Mechanical testing simulated one leg stance, and resultant deformation was measured in bending, torsion, and shortening. In stable fractures, fracture stability was similar to both devices, while in unstable fractures, the larger femoral nail was more stable. Furthermore, the simulation of single leg stance led to a coupled deformation of varus bending, axial shortening, and external rotation, which was dependent on bone geometry.

Adult↗

Synthesis and insertion reactions of the cyclometalated palladium-alkyl complexes Pd(CH(2)CMe(2)-o-C(6)H(4))L(2). Observation of a pentacoordinated intermediate in the insertion of SO(2).

Palladacycles of the type 2, have been synthesized by treatment of the corresponding chloroalkylcomplexes Pd(CH(2)CMe(2)C(6)H(5))ClL(2) (L(2) = (PMe(3))(2), 2a, or 1,5-cyclooctadiene (cod), 2b) with suitable bases, or by simple ligand exchange reactions from the cyclooctadiene derivative 2b. The metallacycles 2 react with activated alkynes and with sulfur dioxide, giving rise to different insertion products.

Journal Article↗

Use of the post-insertion technique to insert peptide ligands into pre-formed stealth liposomes with retention of binding activity and cytotoxicity.

PURPOSE: Simple methods for the large-scale manufacture of ligand-targeted liposomes will be needed if clinical trials are to proceed. We tested a recently developed technology for inserting peptide ligands into preformed Stealth liposomes. Antagonist G-targeted liposomes (PLG) were prepared and loaded with doxorubicin and their cellular association and cytotoxicity were evaluated using the human small cell lung cancer H69 cell line. METHODS: The hexapeptide antagonist G was covalently coupled via a thioether bond to the terminus of polyethylene glycol (PEG) in micelles formed from maleimide-derivatized poly(ethylene glycol) (Mr 2000) distearoylphosphatidylethanolamine followed by transfer into preformed liposomes during a one-step incubation. For cellular association, we used radiolabeled liposomes. Cytotoxicity was evaluated using the MTT in vitro proliferation assay. RESULTS: The postinsertion approach to the formation of peptide-targeted liposomes led to the production of PLG bearing a maximum of approximately 0.3 microg antagonist G/micromol phospholipid. These liposomes had increased cellular association to H69 cells relative to nontargeted liposomes and, when loaded with doxorubicin, they resulted in similar levels of cytotoxicity to those obtained by conventional coupling techniques. CONCLUSIONS: The postinsertion technique is a simple, effective means for the production of biologically active peptide-targeted liposomes.

Binding Sites↗

R-region cDNA inserts in retroviral vectors are compatible with virus replication and high-level protein synthesis from the insert.

Protein expression from retroviral vectors is often highest when the expressed cDNA is driven by the retroviral promoter. However, the typical retroviral vector design places the cDNA downstream of the retroviral packaging signal and far from the retroviral promoter. In an attempt to improve protein production levels from cDNAs expressed in retroviral vectors, we inserted the MyoD or the purine nucleoside phosphorylase (PNP) cDNAs into the R regions of both retroviral LTRs, close to the retroviral promoter and just upstream of the polyadenylation signal present in each long terminal repeat (LTR). These R-region double-copy vectors could be produced in unrearranged form, although the titer was about seven-fold lower than that of typical vectors. R-region positioning of the MyoD cDNA resulted in five-fold higher MyoD expression compared to MyoD expression in a typical vector, whereas PNP expression was not improved. Thus, R-region double-copy vectors provide an alternative vector design that can improve protein expression from some cDNAs.

Animals↗

Transposition in Lactobacillus sakei: inactivation of a second lactocin S operon by the insertion of IS1520, a new member of the IS3 family of insertion sequences.

The analysis of spontaneous bacteriocin-negative mutants has led to the identification and characterization of a new, transpositionally active, insertion sequence of the IS3 family in the lactocin-S-producing Lactobacillus sakei strain L45. The element, which has been designated IS1520, is 1302 bp long with 10 bp perfect inverted repeat ends and generates direct repeats of a trinucleotide of target sequence upon transposition to the lactocin S locus. IS1520 encodes two consecutive, partially overlapping, major ORFs, which are frameshifted in a manner typical of the IS3 family. Despite a low overall DNA sequence similarity, the putative frameshifting region of IS1520 is highly similar to the corresponding region of IS1163, which is a related element previously shown to be active in L. sakei L45.

Amino Acid Sequence↗

Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis.

In this study we established the usefulness of DNA fingerprinting for the epidemiology of tuberculosis on the basis of the DNA polymorphism generated by the insertion sequence (IS) IS986. Although clinical isolates of Mycobacterium tuberculosis displayed a remarkably high degree of restriction fragment length polymorphism, we showed that transposition of this IS element is an extremely rare event in M. tuberculosis complex strains grown either in vitro or in vivo for long periods of time. The M. tuberculosis and Mycobacterium africanum strains tested in this study contained 6 to 17 IS copies. In the Mycobacterium bovis strains, the copy numbers ranged between 1 and 5, and all 27 M. bovis BCG strains investigated invariably contained a single IS copy. This copy was located at a unique chromosomal position, reinforcing the idea that the frequency of IS transposition is very low in M. tuberculosis complex strains. Various microepidemics are described in which each microepidemic corresponds to a particular fingerprint type. The extent of similarity between Dutch and African strains was quantitatively assessed by computer-assisted analysis of DNA fingerprints. The results indicate that M. tuberculosis strains from regions in central Africa, where tuberculosis is highly prevalent, are generally more related to each other than isolates from the Netherlands, where the transmission rate is low and where the majority of the tuberculosis cases are presumed to be the result of reactivation of previously contracted M. tuberculosis infections.

Africa↗

Experience of cardioverter-defibrillators inserted without thoracotomy: evaluation of transvenously inserted intracardiac leads alone or with a subcutaneous axillary patch.

OBJECTIVES: To compare the efficacy of a purely transvenous cardioverter-defibrillator (ICD) system with that of a system with a supplementary subcutaneous patch. To evaluate clinical follow up of these lead arrangements that do not require thoracotomy. DESIGN: A simplified defibrillation protocol to test two different lead arrangements during implantation, with routine clinical follow up after implantation. SETTING: Tertiary referral centre for treatment of arrhythmia. PATIENTS: 22 consecutive patients selected for implantation of an ICD because of life-threatening ventricular arrhythmias (ventricular fibrillation or sustained ventricular tachycardia) of whom 20 entered the test protocol. INTERVENTION: Implantation of an ICD with transvenously inserted intracardiac leads and a subcutaneous patch and assessment of effective defibrillation followed by testing of the purely transvenous approach. MAIN OUTCOME MEASURES: Reproducible conversion of ventricular fibrillation to sinus rhythm at a certain energy level, providing a safety margin of at least 10 J for both lead arrangements. Confirmation of efficacy during clinical follow up (mean 6 months). RESULTS: A transvenous lead system combined with a subcutaneous axillary patch was implanted in 20/22 patients and it provided adequate and acceptable energy levels. In 10/20 tested patients a purely transvenous lead configuration provided an acceptable safety margin as well. Nine patients had clinical recurrences: all these arrhythmias were successfully converted. CONCLUSION: A transvenous lead system was sufficient in 50% of the patients at the time of implantation. Data on long-term clinical follow up of this arrangement are not available. The approach without thoracotomy with a subcutaneous patch is feasible and effective in most patients selected for ICD treatment.

Adult↗

Peripherally inserted central catheters for parenteral nutrition: a comparison with centrally inserted catheters.

BACKGROUND: Central venous access is crucial for the provision of adequate parenteral nutrition (PN). The type of central venous access device (CVAD) has evolved over the past 10 years. The most recent trend has been to use peripherally inserted central catheters (PICCs). This development has occurred without controlled clinical trials. METHODS: Over a 10-year period, the nutrition support service at a single institution has prospectively collected data on CVADs used for providing PN. The types of CVAD used for providing PN were analyzed, and the major complications associated with CVADs, thrombosis and line sepsis, were compared over three different time periods: 1988-1989; 1992-1993; 1996-1997. In addition, complications associated with PICCs were compared with other CVADs. RESULTS: The following were the dominant CVADs over each of the three time periods: 1988-1989: tunneled catheters, 80%; 1992-1993: nontunneled catheters, 46%; and 1996-1997: PICCs, 48%. There was a decreased incidence of sepsis and pneumothorax in 1996-1997 and an increase in severed or leaking catheters and phlebitis. In a comparison of PICC and non-PICC catheters over the past 3 years, there was a trend toward decreasing sepsis with PICC catheters but an increase in malposition, inadvertent removal, and severed or leaking catheters. CONCLUSIONS: PICCs have replaced tunneled and nontunneled central catheters as the most commonly used CVAD for providing PN. PICCs do not result in increased line sepsis or thrombosis but have an increased incidence of local complications such as leaking catheters, phlebitis, and malposition.

Catheterization, Central Venous↗

Repeated postpericardiotomy syndrome following a temporary transvenous pacemaker insertion, a permanent transvenous pacemaker insertion and surgical pericardiotomy.

The postpericardiotomy syndrome is a well-known complication of opening and manipulating the pericardium. The occurrence of this syndrome following transvenous pacemaker insertion is very rare, and only 5 cases have been reported to date. The present patient repeated this syndrome 3 times in a short period following 3 different interventional techniques: a temporary transvenous pacemaker, a permanent transvenous pacemaker and surgical pericardiotomy.

Aged↗