Bioactive fragment of human IL-1beta [163-171] modulates the immune response to synthetic peptides of HIV

The activation of T helper cells specific for viral antigens is critical for antibody production and the generation of cytotoxic T cells during retroviral infection. In this study, we examined the effect of linking HIV peptides with a bioactive fragment of human interleukin-1beta (IL-1beta) (163-171) on the induction of immune response to the peptides. A panel of highly purified synthetic peptides representing defined regions of gp41, Gag and gp120 were used as antigens. Mouse spleen cells primed with the peptide conjugates produced greater proliferation on in vitro stimulation than spleen cells primed with peptide alone. In addition, antibody production as assessed by ELISA was observed after immunization with conjugated peptides but not with peptide alone, indicating B-cell activation. We also found that a high level of IgG2a antibody production correlated with a high level of IFN-gamma production. These findings favor the notion that IL-1beta plays an important role in immune responses. These observations support the formulation and design of synthetic vaccines against HIV using synthetic HIV peptides conjugated with immunomodulators. Such an approach may provide an effective vaccination against other infectious agents.     

Predischarge arrhythmia induction testing of implantable defibrillators may be unnecessary in selected cases

Complete postoperative evaluation of implantable cardioverter-defibrillators (ICDs) before discharge, including arrhythmia induction, has been the standard since their introduction. Whereas the original ICDs provided little telemetered information and used separate pace-sense and defibrillation leads, modern, third-generation devices provide pace-sense function information in addition to other data and are used in conjunction with integrated transvenous endocardial leads that combine pace-sense and defibrillation function. Changes in lead position, which can potentially result in either an inability to detect fibrillation or to terminate it, should be mirrored by changes in resting pace-sense function. Thus, for newer ICDs implanted with integrated endocardial lead systems, it is possible that in at least some cases predischarge arrhythmia inductions can be avoided. Two hundred patients receiving third-generation ICDs in conjunction with integrated transvenous leads were evaluated before discharge. Defibrillation detection or termination problems were seen in 8. Declines in resting R-wave amplitude and pacing impedance were significantly associated with such complications (-7 +/- 5 vs -0.3 +/- 2.3 mV [p <0.0001] and -158 +/- 138 vs -93 +/- 76 omega [p <0.05], for those with vs without complications, respectively), as were gross right ventricular lead migrations on chest x-ray. No patient with a defibrillation complication had an R-wave change of <3 mV. However, 13% of patients without complications had R-wave changes of >3 mV. It is concluded that a pace-sense evaluation of ICDs may be a satisfactory screen to determine those who need to go on to complete testing with arrhythmia induction in selected cases.     

Mutational analysis of CDKN2 (MTS1/p16ink4) in human breast carcinomas

The CDKN2 gene that encodes the cell cycle regulatory protein cyclin-dependent kinase-4 inhibitor (p16) has recently been mapped to chromosome 9p21. Frequent homozygous deletions of this gene have been documented in cell lines derived from different types of tumors, including breast tumors, suggesting that CDKN2 is a tumor suppressor gene involved in a wide variety of human cancers. To determine the frequency of CDKN2 mutations in breast carcinomas, we screened 37 primary tumors and 5 established breast tumor cell lines by single-strand conformation polymorphism analysis. In addition, Southern blot analysis was performed on a set of five primary breast carcinoma samples and five breast tumor cell lines. Two of the five tumor cell lines revealed a homozygous deletion of the CDKN2 gene, but no mutations were observed in any of the primary breast carcinomas. These results suggest that the mutation of the CDKN2 gene may not be a critical genetic change in the formation of primary breast carcinoma.     

Expression of dentin sialoprotein (DSP) and other molecular determinants by a new cell line from dental papillae, MDPC-23

The purpose of this study was to characterize the molecular expression of a spontaneously immortalized and cloned cell line (MDPC-23) derived from 18-19 day CD-I fetal mouse molar dental papillae to determine if these cells were odontoblast-like. Western blots showed that a protein band, at approximately 105 kDa, reacting positively with anti-DSP antibodies and co-migrating with mouse DSP, was present in lysates of cells from passages 7, 37 and 77, in serum-free conditioned medium from passage 37 cells, and in mouse dentin extract. A minor band at 55 kDa was also apparent in cell lysates. Using a cDNA probe for a 486bp mouse DSP coding sequence, DSP or DSP-PP mRNA expression was detected by Northern analysis as well as Southern analysis after RT-PCR in all three passages. It was also shown that in these cells 1,25 (OH)2 vitamin D3 upregulated both osteopontin and osteocalcin mRNA, and dexamethasone downregulated alkaline phosphatase and alpha2(I) collagen mRNA. Thus, MDPC-23 cells express proteins which are common to mineralizing tissue. The expression of DSP and DSP-PP strongly suggests that this cell line is from the odontoblast lineage.     

Hematopoiesis in dogs irradiated with protons in lethal doses with screening of the bone marrow]

The paper presents the results of a 6-year investigation of hemopoiesis of dogs which were exposed to double irradiations (with a 1.5-month interval) with protons at a dose of 350 rad when different parts of the body (head, chest, abdomen, pelvis) were shielded. Throughout the entire period the dogs showed moderate leucopenia and by the end of the investigation insignificant anemia. The dogs irradiated with shielded abdomen displayed disturbances in bone marrow hemopoiesis, whereas other dogs exhibited relative, although transient, normalization. All the dogs showed a significant decrease of erythropoiesis and a relative stability of leucopoiesis as well as a significant elevation of the number of reticulocytes, monocytes and plasmocytes 5.5 year after irradiation.     

A prospective randomised study of local versus general anaesthesia for cataract surgery

A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that the majority of PCBs are likely to interact with AhR in their nonplanar conformations. In addition, we demonstrate that the affinities of PCBs for AhR relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding toxic equivalency factors in animals. The reported methodology is likely to be applicable to other polyhalogenated and mixed polyhalogenated bi- and terphenyls and related xenobiotics; thus, it could minimize the number of in vivo studies in laboratory animals and facilitate the identification of potentially hazardous aromatic xenobiotics.     

Heparin improves oxygenation and minimizes barotrauma after severe smoke inhalation in an ovine model

Inhalation injury is one of the main causes of mortality in burn victims. The tracheobronchial epithelium sloughs and combines with a protein rich exudate to form casts of the airways that can lead to obstruction. We studied the effects of a continuous infusion of heparin on the acute pulmonary injury that occurs after smoke inhalation injury in sheep. Twelve ewes with vascular catheters received a standardized smoke inhalation injury and mechanical ventilation according to protocol for 72 hours. The heparin group (n = 6) received a 400 unit per kilogram bolus of heparin followed by a continuous infusion to maintain the activated clotting time between 250 to 300 seconds. The control group (n = 6) received a saline solution vehicle. Hemodynamics, blood gases and plasma samples for conjugated dienes were taken every six hours. At necropsy, pulmonary tissue was collected for histologic findings, polymorphonuclear neutrophil leukosequestration, wet-to-dry weight ratios and conjugated dienes. PaO2 to FIO2 ratios were improved in the heparin group compared with the control group at 12 to 72 hours after injury, and peak airway pressures were higher in the control group compared with the heparin group. Positive end expiratory pressure requirements were higher in the control group compared with the heparin group. There were significantly fewer airway tracheobronchial casts as determined by our tracheobronchial casts scoring system (2.4 +/- 0.4 versus 0.67 +/- 0.21) and confirmed by histologic examination. Pulmonary blood-free wet-to-dry weight ratios were higher in the control group compared with the heparin group (6.4 +/- 0.5 versus 5.2 +/- 0.1; p < 0.05). There were no differences in pulmonary tissue or plasma conjugated dienes; likewise, pulmonary leukosequestration was unaffected by heparin. Heparin decreases tracheobronchial cast formation, improves oxygenation, minimizes barotrauma and reduces pulmonary edema in an ovine model of severe smoke inhalation injury. Heparin does not reduce oxygen free radical activity after smoke inhalation injury.