Integrilin prevents prolonged bleeding times after cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass reduces platelet number and function, increases postoperative bleeding time, and is the major, unsolved cause of nonsurgical bleeding after open heart operations. Temporary inhibition of platelet function during cardiopulmonary bypass (platelet anesthesia) protects platelets and reduces postoperative bleeding time and bleeding. METHODS: Integrilin, a short-acting, reversible platelet glycoprotein IIb/IIIa inhibitor was studied in 28 baboons that had 60 minutes of normothermic cardiopulmonary bypass using peripheral cannulas. A control group, two groups that received different doses of Integrilin, and a group that received a combination of Integrilin and low-dose Iloprost were studied. Blood samples for platelet count, aggregation to adenosine diphosphate, beta-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, and fibrinopeptide A were obtained at seven time points. Template bleeding times were measured before and at five intervals after cardiopulmonary bypass. RESULTS: Both doses of Integrilin and the combination of Integrilin and Iloprost significantly protected platelet number, inhibited the response to adenosine diphosphate, and reduced postoperative bleeding times, but they did not reduce beta-thromboglobulin release except in the high-dose Integrilin group. Thrombin formation and activity were qualitatively, but not significantly, reduced in all treatment groups. Bleeding times were not significantly different from baseline at the time protamine was given in the combination group and 60 minutes after protamine administration in all treatment groups. CONCLUSIONS: Integrilin alone or in combination with Iloprost significantly reduces platelet activation during cardiopulmonary bypass and produces normal or near-normal bleeding times at the time protamine is given.     

A Ca2+-activated whole-cell Cl- conductance in human placental cytotrophoblast cells activated via a G protein

Evidence now suggests that some people can exert some degree of control over seizure initiation and inhibition. In order to explore this further, 79 young people with epilepsy, attending specialist residential schools, were interviewed regarding awareness of seizure precipitants; recognition of seizure warnings; attempts at seizure inhibition, and ways of self-inducing seizures. Questionnaires with the same content were completed by residential care staff. Results show that many subjects claimed to identify seizure precipitants (63.3%), experienced warnings (70.9%), and had developed means of trying to inhibit seizure occurrence (50.6%). However, in each instance, staff reports were much lower (56.9%, 47.2%, and 22.2%, respectively), and one-to-one concordance was poor. A larger than expected percentage of self-induction was reported for both subjects (8.9%) and staff (9.7%). The implication of these results for both the investigation and treatment of epilepsy are discussed further.     

Epitope mapping using histidine-tagged protein fragments: application to Escherichia coli RNA polymerase sigma 70

The pathogenic Neisseria have exploited the processes of horizontal DNA transfer and genetic recombination as mechanisms for the generation of extensive protein variation and modulation of gene expression. Localized recombinations have been well documented in members of multigene families as have alterations in short repetitive sequences. Here we report an analysis of the chromosomal structure of a defined lineage of Neisseria gonorrhoeae strain MSl1 pilin variants. This study reveals the occurrence of large rearrangements, including the amplification of a 26 kb region and an inversion involving more than a third of the chromosome. Additionally, a restriction site polymorphism that correlates with pilin expression has been observed. These findings highlight the flexibility of the gonococcal genome.     

Transcriptional and post-transcriptional regulation of interleukin-8

We have previously shown that vaccines expressing virus-derived cytotoxic-T-lymphocyte (CTL) epitopes as short minigenes can confer effective protection against virus challenges, and here we extend these studies to the bacterium Listeria monocytogenes. Host defense against this important human pathogen appears largely T cell mediated, and a nonamer CTL epitope from the listeriolysin O (LLO) protein has been identified in BALB/c mice. We have synthesized this nonamer as a minigene, expressed it in a recombinant vaccinia virus (VV-list), and used this to immunize mice. Memory CTLs cultured from VV-list-immunized mice specifically lyse target cells pulsed with a nonamer peptide identified at LLO amino acid residues 91 to 99. Four weeks postimmunization, mice were challenged with L. monocytogenes. By day 6 following challenge with a sublethal dose of L. monocytogenes, mice immunized with VV-list showed a approximately 2,000- to 6,000-fold reduction in bacteria CFU in the spleen and liver. At this time point, with control mice, bacterial were readily detectable by Gram stain of the liver but were undetectable in the VV-list-immunized animals. Additionally, when a normally lethal dose of bacteria was given, death was delayed in VV-list-immunized animals. This study has demonstrated that a single immunization with a recombinant vaccinia virus bearing only nine amino acids from a bacterial pathogen can induce specific CTLs able to confer partial protection against bacterial challenge.     

DNA replication is completed in Saccharomyces cerevisiae cells that lack functional Cdc14, a dual-specificity protein phosphatase

A 35-year-old man affected with pulmonary sarcoidosis had a 12-year history of fatigue and pain in the limbs, with normal neurological examination, except for diffusely absent deep tendon reflexes. Muscle biopsy samples showed multiple noncaseating granulomas, most prominent around the intramuscular nerves, with predominance of CD4+ cells. Intramuscular nerve bundles surrounded by granulomas were immunolabelled with laminin alpha1, alpha2, beta1 and gamma1 chain, and collagen IV. Sural nerve biopsy samples were normal. This patient showed a unique histopathological pattern of sarcoid neuromyopathy characterized by distribution of granulomas or infiltrating cells around intramuscular nerve fibers. The clinical picture, restricted to nonspecific symptoms of fatigue and myalgia, and loss of deep tendon reflexes, correlated well with the selective localization of sarcoid lesions in contiguity with the intramuscular nerves. To our knowledge, this peculiar clinico-pathological correlation has not been reported previously.     

Effect of oxytocin on transepithelial transport of water and Na+ in distinct ventral regions of frog skin (Rana catesbeiana)

Thoracic, abdominal, and pelvic fragments of ventral skin of Rana catesbeiana were analysed regarding the effect of oxytocin on: (1) transepithelial water transport; (2) short-circuit current; (3) skin conductance and electrical potential difference; (4) Na+ conductance, the electromotive force of the Na+ transport mechanism, and shunt conductance; (5) short-circuit current responses to fast Na+ by K+ replacement in the outer compartment, and (6) epithelial microstructure. Unstimulated water and Na+ permeabilities were low along the ventral skin. Hydrosmotic and natriferic responses to oxytocin increased from thorax to pelvis. Unstimulated Na+ conductance was greater in pelvis than in abdomen, the other electrical parameters being essentially similar in both skin fragments. Contribution of shunt conductance to total skin conductance was higher in abdominal than in pelvic skin. Oxytocininduced increases of total skin conductance, Na+ conductance, and shunt conductance in pelvis were significantly larger than in abdomen. An oscillatory behaviour of the short-circuit current was observed only in oxytocin-treated pelvic skins. Decrease of epithelial thickness and increase of mitochondria-rich cell number were observed from thorax to pelvis. Oxytocin-induced increases of interspaces were more conspicuous in pelvis and abdomen than in thorax.     

Regression of established mouse leukemia by GM-CSF-transduced tumor vaccine: implications for cytotoxic T lymphocyte responses and tumor burdens

This study investigated the therapeutic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on a mouse leukemia model. By using a retroviral vector, mouse GM-CSF cDNA was transduced into a highly tumorigenic T leukemia cell line, RL male 1. Injection of GM-CSF-secreting RL male 1 cells into syngeneic BALB/c mice elicited protective immunity in the animals, which could regress preestablished tumors introduced either by a subcutaneous or in an intravenous route. However, the therapeutic effects were less prominent in the mice inoculated with a large tumor load or in mice treated later. Winn tests further demonstrated that the splenocytes from the late-treated group conferred poorer protective effects in terms of reducing the growth of parental RL male 1 cells in naive mice than the splenocytes from the early-treated group. Nonetheless, upon stimulation in vitro, the activity of tumor-specific cytotoxic T lymphocytes (CTL) was comparable in the splenocytes of both groups of mice. Histological analysis also indicated that the CD8+ T cells appeared as early as 3 days following vaccination at the vaccine sites and at the tumor sites in both groups of mice. Above observations implied that the T cells in the animals bearing large tumors appeared to be in a state of suppression or anergy. Systematic histological analyses for 2 weeks provided further insight into various infiltrates at the vaccine sites and at the tumor sites in response to the inoculation of GM-CSF-secreting tumor vaccine.     

Seroconversion of a trivalent measles, mumps, and rubella vaccine in children aged 9 and 15 months

The serological response to MMR vaccine was evaluated in 109 9-month-old infants having no history of measles vaccination, and in 98 15-month-old children who had received monocomponent measles immunisation at 9 months. The combined vaccine contained Schwarz, Urabe Am9, and Wistar RA 27/3 live attenuated virus strains. Preimmunisation antibody levels were extremely low for the 9-month-old children, indicating that maternally-transmitted antibodies do not persist at this age. In the case of mumps, preimmunisation antibody levels were significantly higher in the 15-month-old than in the 9-month-old group. A difference between groups in terms of postimmunisation antibody titres was observed only for rubella, with titres being significantly higher in the older group. Seroconversion rates were high in both groups and no serious events attributable to vaccination were observed. The MMR vaccine can thus be administered to children as young as 9 months of age. Evidence for the efficacy of a two-dose schedule, i.e. at 9 and 15 months, is presented.     

Surgical treatment of a septic dentigerous cyst in a goat

A slowly growing lesion of the rostral mandible of a goat was diagnosed to be a septic dentigerous cyst. The lesion was treated surgically to remove one displaced tooth and debride the cystic cavity, and systemic antibiotic therapy was applied. Thirty-four weeks later the goat was clinically and radiographically improved and the problem had not recurred.