Deaths from burns a major cause of surgical paediatric deaths in Zambia.
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Biomedical subjects
Publications and source records attributed to M Y Ma.
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To investigate law of FOS protein induced by myocardial ischemia reperfusion (MI/R) in acute period, a model in 20 anaethetized SD rats was established. Rats with normal and ischemia were used as control groups. Specimens were studied immunohistochemically with c-fos antibody. After ischemia 20 minutes, followed by 30 minutes reperfusion, the area of MI/R showed nuclei of myocytes positive staining in cryosection slides. In C2 group, the area showed nuclei of myocytes (37.76% +/- 9.66%) positive staining weakly. In C3 group, nuclei of cardiac myocytes(40.34% +/- 3.32%) was significantly positive. In C4 group it began to attenuate(35.36% +/- 4.81%). The myocardium in normal and ischemic control groups showed negative staining. No changes were seen with HE staining. Our data indicated that immunohistochemical method may reveal acute MI/R injury of ischemia 20 min and reperfusion 30 min with anti-FOS protein staining and there is problely a peak between 60-120 min after reperfusion. It is possible that the method be used to diagnose sudden cardiac death in forensic medicine.
External guide sequences (EGSs) are short oligoribonucleotides, which are designed to bind to a given RNA target and form a precursor tRNA-like complex. This complex can be recognized by ribonuclease P (RNase P), resulting in specific cleavage of the RNA target. To explore the potential of this class of compounds as therapeutic agents and valuable tools for gene function analysis, various chemical modifications were introduced into an all-RNA EGS molecule to confer nuclease resistance. In particular, 2'-O-methyl substitutions were incorporated into the entire sequence (i.e., A-stem, D-stem, and T-stem) except the T-loop region without loss of cleavage-inducing activity. Replacement of rU (position 54) and rC (position 56) in the T-loop with their 2'-O-methyl counterparts caused pronounced decrease in activity. Moreover, phosphorothioate backbone modification of the T-loop did not provide sufficient protection against endonucleolytic attack at the ribopyrimidine residues. Systematic modification of the T-loop with a variety of modified nucleosides and the addition of a 3'-3' inverted T at the 3'-end have generated several lead EGS prototypes, which not only exhibit wild-type activity in inducing RNase P-mediated target cleavage as compared with the all-RNA control but also remain intact in human serum for more than 24 hours. These results should provide useful insights into the design and development of oligonucleotide-based EGSs as potential regulators of gene expression.
3-ethoxy-1,2,4-dithiazoline-5-one (EDITH) was recently introduced as an efficient sulfurizing reagent for solid-phase oligonucleotide synthesis. The successful syntheses were performed using standard base protecting groups (i.e. benzoyl for A and C, isobutyryl for G), which required deprotection in concentrated ammonium hydroxide at 55 degrees C for 15-18 h. We have explored the possibility of using EDITH in combination with fast deprotection chemistry(e.g. Expedite Chemistry using tert -butylphenoxy acetyl as a base protecting group). Surprisingly, poor synthesis performance was observed when syntheses were conducted with EDITH, Expedite Chemistry and standard synthesis cycle (i.e. Coupling-Thio-Cap). Potential G modification seemed to be the source of incompatibility since sequences containing no G or carrying isobutyryl- protected G residues could be synthesized with high efficiency. However, the deleterious G modification can be readily eliminated by inserting a capping step before the sulfurization reaction. Oligomers prepared with the Coupling-Cap-Thio-Cap cycle contained few phosphodiester contaminants as measured by31P-NMR, anion-exchange HPLC and MALDI-TOF mass spectrometry. In addition to reducing deprotection time, this new combination also provides a mild method for the preparation of certain phosphorothioate oligomers that may be sensitive to prolonged ammonia treatment (e.g. thioated RNAs).
Soon after antimicrobial drugs became available, it was recognized that they were being overused and misused. Reasons for concern about the inappropriate use of antimicrobials include the emergence of resistant nosocomial bacteria, which have been identified in every hospital nationwide. The presence of resistant nosocomial bacteria presents the physician with a clinical problem and increases the cost of therapy. It is clear that methods need to be implemented to help physicians improve prescribing of antimicrobial agents. As health care practitioners in all fields strive to make patient care more cost-effective, one observation has become evident: The successfully treated patient consumes fewer resources and subsequently costs the hospital less than an otherwise similar, unsuccessfully treated patient. The goal in the 1990s is to provide optimal, cost-effective care for patients without compromising quality. This goal can be achieved by collaborative efforts of physicians, pharmacists, and microbiologists working together as a team to promote quality patient care.
Double-stranded oligodeoxyribonucleotides or single-stranded oligoribonucleotides with specific secondary structure have been proposed as potential antagonists to target nucleic acid-binding proteins (the sense approach). A major limitation of this strategy is that these derivatives are generally considered to be too large for pharmaceutical applications. We have developed a synthetic linker approach whereby nucleic acid duplexes of a much smaller size (miniduplexes) can be generated directly from a standard oligonucleotide synthesis. In this approach, four synthetic linkers (derivatized respectively from 1,9-nonanediol, triethylene glycol, 1,3-propanediol, and hexaethylene glycol) of different length and hydrophobicity were designed and incorporated into a model RNA molecule based on the TAR stem-loop structure of HIV-1. Their thermal stabilities were evaluated by measuring denaturation profiles (Tm measurements). These linker-derivatized RNA molecules were then assessed for their ability to bind to either a full-length protein (HIV-1 Tat protein) or a short peptide (Tat-derived peptide) through RNA mobility shift assays. Results from this study indicate that such modified miniduplex structures retain full binding activity relative to that of the wild-type sequence (Kd values), while Tm values were increased by 24-31 degrees C compared to an open duplex of the same length. This system provides a new direction in the use of nucleic acid miniduplexes as a novel class of oligonucleotide analogues for both fundamental research and possible therapeutic applications.
A collaborative exploration of the political realities and implications faced by self-identified Asian Pacific Islander lesbian and gay writers. Mixed-genre piece combining the essay and dialogue form, it contains sections co-written as well as individual pieces by the authors. The issues touched upon through this discussion are: available community-based and mainstream publishing venues, development of community-based writing, relation between grassroots political organizing and writing, API and lesbian/gay identity issues, internalized racism and homophobia, and other barriers for API lesbian and gay writers.
Interaction between the human immunodeficiency virus type 1 (HIV-1) trans-activator Tat and its cis-acting responsive RNA element TAR is necessary for activation of HIV-1 gene expression. We investigated the hypothesis that the essential uridine residue at position 23 in the bulge of TAR RNA is involved in intramolecular hydrogen bonding to stabilize an unique RNA structure required for recognition by Tat. Nucleotide substitutions in the two base pairs of the TAR stem directly above the essential trinucleotide bulge that maintain base pairing but change sequence prevent complex formation with Tat in vitro. Corresponding mutations tested in a trans-activation assay strongly affect the biological activity of TAR in vivo, suggesting an important role for these nucleotides in the Tat-TAR interaction. On the basis of these data, a model is proposed which implicates uridine 23 in a stable tertiary interaction with the GC pair directly above the bulge. This interaction would cause widening of the major groove of the RNA, thereby exposing its hydrogen-bonding surfaces for possible interaction with Tat. The model also predicts a gap between uridine 23 and the first base pair in the stem above, which would require one or more unpaired nucleotides to close, but does not predict any other role for such nucleotides. In accordance with this prediction, synthetic propyl phosphate linkers of equivalent length to 1 or 2 nucleotides, were found to be fully acceptable substitutes in the bulge above uridine 23, demonstrating that neither the bases nor the ribose moieties at these positions are implicated in the recognition of TAR RNA by Tat.
In a 710-bed teaching hospital, the infectious disease section and pharmacy service initiated a joint programme to control and monitor the use of third-generation cephalosporins (TGC): cefotaxime, moxalactam and cefoperazone. The policy requires that an infectious disease physician approve the use of a TGC prior to its administration. This retrospective study sought to assess the pattern of utilization of these agents. From January to December 1983, 109 patient courses of cefotaxime (CT), moxalactam (MX), and cefoperazone (CP) were tabulated. Records from 92 patient courses were available for review (84.4%). The preliminary data show that 46.7% of TGC were used empirically to treat suspected infections without culture and sensitivity data, while 50.0% were used to treat various infections (central nervous system, pulmonary, wound, abdominal, biliary, urinary and blood) after culture and sensitivities were known. Only 3.3% of the TGC were used for surgical prophylaxis. In the empirical treatment group, the leading indications for use of TGC were central nervous system (CT = 40.0%, MX = 48.0%) and biliary (CP = 23.1%) infections. In the treatment group with culture and sensitivity data, the primary uses of TGC were for the treatment of Gram-negative pulmonary (MX = 28.0%, CP = 19.2%) and wound (CP = 15.4%) infections. This study shows that physician and pharmacy control does not eliminate empirical treatment with TGC; but it does narrow their use to situations in which their properties are best exploited.
The development of resistance of gram-negative bacilli, which are common nosocomial pathogens, is an increasing problem. It is generally accepted that this resistance may directly reflect the frequency of use of various antimicrobial agents. Because our institution experienced in 1976 a dramatic change in the pattern of antimicrobial use, primarily a marked decrease in prescribing cephalosporins, we attempted to evaluate retrospectively the effects of this change upon the resistance of gram-negative bacilli that are common nosocomial pathogens. Susceptibilities of Klebsiella and Providencia spp., Pseudomonas aeruginosa, and Serratia marcescens were determined for the years 1975 to 1979. Not unexpectedly, we observed a substantial decrease in cephalosporin resistance. An unexpected finding was a decrease in aminoglycoside resistance, despite increased use of these agents. The possibility that decreased cephalosporin use may lead to decreased aminoglycoside resistance is an intriguing and provocative thesis which can only be speculative at this time but which would seem worthy of additional formal investigation.
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