Acidic lipids associated with the local mechanism of calcificaiton: a review

Two current areas of research on hard tissues have focused upon acidic lipids associated with the local mechanism of calcification and the presence of matrix vesicles as the loci for initial mineralization. Data which show that acidic phospholipids are a component of the vesicle membrane provide a common denominator between these two areas. Furthermore, studies on vertebrate, microbial and synthetic lipoprotein calcification indicate that acidic phospholipids play a pivotal role in the local mechanism. Through a sequence of initial Ca2++ binding followed by desolvation and ion concentration, the acidic phospholipid rich membrane provides an environment in which calcification can be facilitated. A proposed mechanism includes in additon to Ca2++ binding, the formation of (CaHPO4)2 dimers and their condensation into a Ca9 (PO4)6 unit bound to the membrane. The bound unit functions as a nucleus for the formation of additonal units to form an amorphous calcium phosphate cluster. Conversion to crystalline apatite would require dehydration of the environment, either by mineral build up exceeding the hydrophobic domain or by breakdown of the membrane.     

Recovery of postischemic contractile function is depressed by antegrade warm continuous blood cardioplegia

Drug-abusing (n = 25) and nonusing (n = 55) pregnant women from a publicly supported prenatal clinic were tested for level of social support and of pregnancy anxiety during the last half of pregnancy. Differences found between the groups were fewer than expected. Drug abusers did not differ from nonusers in overall level of social support or in Appraisal, Belonging, or Tangible subscales. Abusers were found to report lower levels of self esteem; lower self esteem was predicted by drug abuse, having more children and lower socioeconomic status. Drug abusers did not differ from nonusers in their overall feelings of pregnancy anxiety, but they did indicate higher fears for themselves and for the baby, and there was a tendency for higher depression and withdrawal.     

Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines

We have studied 18 participants in phase I/II clinical trials of recombinant gp120 (rgp120) subunit vaccines (MN and SF-2) who became infected with human immunodeficiency virus type 1 (HIV-1) during the course of the trials. Of the 18 individuals, 2 had received a placebo vaccine, 9 had been immunized with MN rgp120, and seven had been immunized with SF-2 rgp120. Thirteen of the 18 infected vaccinees had received three or four immunizations prior to becoming infected. Of these, two were placebo recipients, six had received MN rgp120, and five had received SF-2 rgp120. Only 1 of the 11 rgp120 recipients who had multiple immunizations failed to develop a strong immunoglobulin G antibody response to the immunogen. However, the antibody response to rgp120 was transient, typically having a half-life of 40 to 60 days. No significant neutralizing activity against the infecting strain was detected in any of the infected individuals at any time prior to infection. Antibody titers in subjects infected despite vaccination and in noninfected subjects were not significantly different. Envelope-specific cytotoxic T-lymphocyte responses measured after infection were infrequent and weak in the nine vaccinees who were tested. HIV-1 was isolated successfully from all 18 individuals. Sixteen of these strains had a non-syncytium-inducing (NSI) phenotype, while two had a syncytium-inducing (SI) phenotype. NSI strains used the CCR5 coreceptor to enter CD4+ cells, while an SI strain from one of the vaccinees also used CXCR4. Viruses isolated from the blood of rgp120 vaccinees were indistinguishable from viruses isolated from control individuals in terms of their inherent sensitivity to neutralization by specific monoclonal antibodies and their replication rates in vitro. Furthermore, genetic sequencing of the env genes of strains infecting the vaccinees did not reveal any features that clearly distinguished these viruses from contemporary clade B viruses circulating in the United States. Thus, despite rigorous genetic analyses, using various breakdowns of the data sets, we could find no evidence that rgp120 vaccination exerted selection pressure on the infecting HIV-1 strains. The viral burdens in the infected rgp120 vaccine recipients were also determined, and they were found to be not significantly different from those in cohorts of placebo-vaccinated and nonvaccinated individuals. In summary, we conclude that vaccination with rgp120 has had,to date, no obvious beneficial or adverse effects on the individuals we have studied.     

Development of a novel, rapid processing protocol for polymerase chain reaction-based detection of bacterial infections in synovial fluids

We describe the development of a molecular detection system designed for use with synovial fluid (SF)-based infections. The methodology employs a lysis/extraction procedure that effectively disrupts microorganisms allowing for release of the microbial DNA and its amplification by polymerase chain reaction (PCR). We tested the effectiveness of adding a mixed-bed, ion-exchange resin to the extract to remove PCR inhibitory components present in the SF. After centrifugation to separate the resin, DNA contained in the supernatant is subjected to PCR using oligonucleotide primers designed for broad-spectrum microorganism detection. Amplification products are analyzed by agarose gel electrophoresis and/or DNA hybridization methodology. We report here the detection sensitivity and specificity of the protocol using SF inoculated with Escherichia coli and Staphyloccocus aureus. We have applied this new methodology to clinical SF specimens with results superior to standard laboratory culturing assays.     

Stereospecific actions of the inhalation anesthetic isoflurane at the GABAA receptor complex

To overcome problems associated with Western blotting of denatured proteins, we have used quantitative immunoelectrophoretic techniques to perform functional analysis of the Neisseria gonorrhoeae common antigen. Using these techniques, we show (a) that Neisseria gonorrhoeae expresses an antigen that is cross-reactive with the common antigen of Pseudomonas aeruginosa and Legionella micdadei and with the GroEl-like protein of Chlamydia, and (b) that this N. gonorrhoeae common antigen has lectin-like activity and can be precipitated with three different sugars immobilized on agarose beads: alpha-D-glucosamine, maltose and fucose.     

Potential for an external vaginal antiitch cream containing benzocaine to cause methemoglobinemia in healthy women

OBJECTIVES: Our purpose was to assess the potential for an external vaginal antiitch cream (20% benzocaine, 3% resorcinol) to significantly increase levels of methemoglobin above normal in healthy women. STUDY DESIGN: Fifty-five women reporting external vaginal itch were recruited for the study. Each patient was used as her own control with methemoglobin levels being measured before and after use of the cream. Women were instructed to apply a 1-inch strip of cream by fingertip to the external genital area three or four times a day for 7 consecutive days. RESULTS: There were no significant differences in methemoglobin levels before and after use or in levels from a subgroup of women aged > 50 years compared with levels in a younger population. CONCLUSIONS: This preparation appears to be safe when used as directed; however, the results cannot be extrapolated to the very young. Nevertheless, lavish or frequent application over wide areas of excoriation might lead to toxic concentrations and methemoglobinemia. Therefore patients with serious vaginal disease should be advised against self-treatment beyond the 7-day limit imposed by the Food and Drug Administration for over-the-counter external analgesic medications.