Infant immunization with pneumococcal CRM197 vaccines: effect of saccharide size on immunogenicity and interactions with simultaneously administered vaccines

Six pentavalent pneumococcal conjugate vaccines (Pn-CRM197) were evaluated among 400 infants. The vaccines differed in saccharide chain length (oligosaccharide [OS] or polysaccharide [PS]) and saccharide quantity (0.5, 2, or 5 microg). Subjects were randomized into groups 1-6 (Pn-CRM197 recipients) or 7 (controls) for immunization at 2, 4, and 6 months of age. Pn-CRM197 were well tolerated and elicited mean antibody concentrations that exceeded those in controls for all 5 capsular serotypes. PS formulations were generally more immunogenic than their OS counterparts. For PS vaccines, a dose-response was documented (5 microg > 2 microg > 0.5 microg), but the differences between the 5- and 2-microg formulations were insignificant. The mean anti-PRP antibody concentration was significantly higher among Pn-CRM197 recipients. It is concluded that PS vaccines are more immunogenic than OS vaccines. The improved immunogenicity from Haemophilus type b oligosaccharide conjugate (HbOC) vaccine when given with Pn-CRM197 suggests that a decreased dose of HbOC vaccine may be sufficient to elicit protection.     

Simian immunodeficiency virus (SIV)-specific CTL in cerebrospinal fluid and brains of SIV-infected rhesus macaques

Simian immunodeficiency virus (SIV)-specific CD8+ CTL were isolated from blood, cerebrospinal fluid, and brains of rhesus macaques infected i.v. with SIV. CTL were found as early as 1 wk postinfection and their appearance correlated with a decrease of viral Ag (p27) found in the blood. CTL isolated from cerebrospinal fluid and/or brain often recognized different viral proteins than CTL isolated from blood, suggesting either a unique migratory pattern to the central nervous system or a difference in activation/retention of lymphocytes in these compartments.     

Smoking screening and management in primary care practices

This study examined how pain coping efficacy and pain coping strategies were related to reports of pain during mammography. Subjects were 125 women over the age of 50 undergoing screening mammograms. Prior to their mammogram, all subjects completed the Coping Strategies Questionnaire (CSQ) to assess how they cope with day-to-day pain experiences. Ratings of pain during the mammogram were collected using a 6-point pain/discomfort scale, a 100-mm Visual Analog Scale, the adjective checklist of the McGill Pain Questionnaire, and the Brief Pain Inventory. Up to 93% of the women reported the mammogram examination was painful. On average, women rated the mammography pain in the low to moderate range. Considerable variability in pain ratings was found, however, with some women reporting severe pain and others reporting little or no pain. Correlational analyses were conducted to examine how coping efficacy (CSQ ratings of ability to decrease pain and ability to control pain) and coping strategies (CSQ pain coping strategy subscales) related to variations in pain report. There was a pattern for ratings of ability to decrease pain to be related to lower ratings of current mammography pain. Women who rated their ability to decrease pain as high reported lower average levels of mammography pain, lower ratings on the mammography pain/discomfort scale, and were much more likely to report having had lower levels of pain during their last mammogram. These findings suggest that women who rate their coping efficacy in decreasing day-to-day pain as low may be at higher risk for having a painful mammogram. Individual pain coping strategies were not generally correlated with pain ratings. Behavioral interventions (e.g., patient controlled breast compression) and cognitive therapy interventions (e.g., training in the use of calming self-statements or distraction techniques) designed to increase coping efficacy potentially could be useful in reducing pain in women who are at risk for pain during mammography.     

Lymphomas with testicular localisation show a consistent BCL-2 expression without a translocation (14;18): a molecular and immunohistochemical study

Rabbits were immunised with stage 1 and stage 2 soluble haemagglutinins (sHA) of Helicobacter pylori strain NCTC 11637 and with rabbit erythrocytes coated with stage 1 sHA. After adsorption of stage 1 sHA on erythrocytes, SDS-PAGE analysis showed that 4 major protein bands were removed from the preparation. The anti-sHA coated erythrocyte serum had the highest HA inhibition titre of 16. Crossed immunoelectrophoresis of the stage 1 sHA, against stage 1 and 2 antisera showed multiple precipitin arcs; however, the anti-sHA coated erythrocyte serum produced only two arcs. One arc produced by the anti-stage 2 serum was absent with the anti-stage 1 serum. This arc could have been produced against a 20 kDa polypeptide which was absent in the stage 1 sHA. The other arc was stronger when compared with that produced by anti-stage 1 serum. These two arcs corresponded to the two arcs produced by the anti-sHA coated erythrocyte serum, which had the highest inhibition titre. The two arcs were markedly reduced in crossed immunoelectrophoresis with an adsorbed stage 1 sHA preparation, which indicates that these arcs were produced against the sHAs.     

Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis

Extracellular deposition of amyloid fibrils is responsible for the pathology in the systemic amyloidoses and probably also in Alzheimer disease [Haass, C. & Selkoe, D. J. (1993) Cell 75, 1039-1042] and type II diabetes mellitus [Lorenzo, A., Razzaboni, B., Weir, G. C. & Yankner, B. A. (1994) Nature (London) 368, 756-760]. The fibrils themselves are relatively resistant to proteolysis in vitro but amyloid deposits do regress in vivo, usually with clinical benefit, if new amyloid fibril formation can be halted. Serum amyloid P component (SAP) binds to all types of amyloid fibrils and is a universal constituent of amyloid deposits, including the plaques, amorphous amyloid beta protein deposits and neurofibrillary tangles of Alzheimer disease [Coria, F., Castano, E., Prelli, F., Larrondo-Lillo, M., van Duinen, S., Shelanski, M. L. & Frangione, B. (1988) Lab. Invest. 58, 454-458; Duong, T., Pommier, E. C. & Scheibel, A. B. (1989) Acta Neuropathol. 78, 429-437]. Here we show that SAP prevents proteolysis of the amyloid fibrils of Alzheimer disease, of systemic amyloid A amyloidosis and of systemic monoclonal light chain amyloidosis and may thereby contribute to their persistence in vivo. SAP is not an enzyme inhibitor and is protective only when bound to the fibrils. Interference with binding of SAP to amyloid fibrils in vivo is thus an attractive therapeutic objective, achievement of which should promote regression of the deposits.     

Catheter-based radiotherapy to inhibit restenosis after coronary stenting

BACKGROUND: In animal models of coronary restenosis, intracoronary radiotherapy has been shown to reduce the intimal hyperplasia that is a part of restenosis. We studied the safety and efficacy of catheter-based intracoronary gamma radiation plus stenting to reduce coronary restenosis in patients with previous restenosis. METHODS: Patients with restenosis underwent coronary stenting, as required, and balloon dilation and were then randomly assigned to receive catheter-based irradiation with iridium-192 or placebo. Clinical follow-up was performed, with quantitative coronary angiographic and intravascular ultrasonographic measurements at six months. RESULTS: Fifty-five patients were enrolled; 26 were assigned to the iridium-192 group and 29 to the placebo group. Angiographic studies were performed in 53 patients (96 percent) at a mean (+/-SD) of 6.7+/-2.2 months. The mean minimal luminal diameter at follow-up was larger in the iridium-192 group than in the placebo group (2.43+/-0.78 mm vs. 1.85+/-0.89 mm, P=0.02). Late luminal loss was significantly lower in the iridium-192 group than in the placebo group (0.38+/-1.06 mm vs. 1.03+/-0.97 mm, P=0.03). Angiographically identified restenosis (stenosis of 50 percent or more of the luminal diameter at follow-up) occurred in 17 percent of the patients in the iridium-192 group, as compared with 54 percent of those in the placebo group (P= 0.01). There were no apparent complications of the treatment. CONCLUSIONS: In this preliminary, short-term study of patients with previous coronary restenosis, coronary stenting followed by catheter-based intracoronary radiotherapy substantially reduced the rate of subsequent restenosis.     

Tumor-specific pyruvate kinase isoenzyme M2 involved in biochemical strategy of energy generation in neoplastic cells

The first observation that in vitro fertilization (IVF) was useful for treating oligozoospermia and oligoasthenozoospermia was reported by Fishel and Edwards in 1982. This was followed by a series of cases indicating the value of IVF in such cases. Conventional IVF has been modified and refined to achieve increased rates of conception in cases of male factor infertility. Methods such as high insemination concentration IVF for the treatment of teratozoospermia and microscopic IVF for the treatment of oligozoospermia have had some impact on fertilization and pregnancy rates; however, reports of success are varied. The recent advent of micromanipulation and, in particular, intracytoplasmic sperm injection (ICSI) has overshadowed the use of these modified IVF procedures. Because of the high fertilization and pregnancy rates achieved with ICSI, other micromanipulation techniques (subzonal insemination and partial zona dissection) have been abandoned; there have also been suggestions that other more conventional techniques, i.e. IVF, should also be abandoned and that ICSI become the sole technique for the treatment of infertility. The rapid increase in the number of centres using ICSI has led to extreme pressure for individual units to achieve high fertilization and pregnancy rates and there is a temptation to assign all patients to ICSI treatment. It is important that, in this highly competitive environment, new techniques are not applied haphazardly and reduced to the mere injection of gametes and achievement of pregnancy regardless of the cause of infertility. In his 1986 IVF--Historical Perspective, Fishel quoted Auguste Comte: 'to understand science it is necessary to know its history'. IVF has much recent history in animal and also human work. Although ICSI is the most significant therapeutic advance in male infertility treatment, its application to human IVF is only 4 years old, with a paucity of animal studies on which to rely. For this reason IVF still plays a very important role in the treatment of male factor infertility and should only be ruled out when it has failed previously or the number of available sperm is limited.