Induction of cross-reactive antibodies by immunization of healthy adults with types Ia and Ib group B streptococcal polysaccharide-tetanus toxoid conjugate vaccines

Types Ia and Ib group B streptococcal (GBS) capsular polysaccharides (PSs) are structural isomers but are antigenically distinct. Immunization of healthy adults with GBS type Ia PS-tetanus toxoid (Ia-TT) or Ib-TT glycoconjugate vaccines induced > or = 4-fold increases in specific immunoglobulin G to the heterologous PS in more than two-thirds of subjects. Ib-TT vaccine-induced IgG bound with substantially higher affinity to homologous (Ib) than to heterologous (Ia) PS and promoted opsonophagocytic killing of GBS type Ib but not type Ia organisms. The failure of the Ib-TT- and Ia-TT-induced human antibodies to kill bacteria of the cross-reactive serotype contrasts with the results of previous studies in animals. Inhibition enzyme-linked immunosorbent assays demonstrated that Ib-TT-induced IgG to the homologous PS bound mainly to native Ib PS, whereas the cross-reactive antibodies recognized both native and derivative PSs. These results indicate that GBS Ia and Ib PSs should be included in a multivalent conjugate vaccine to prevent GBS disease.     

Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis

Objectives

The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR.

Immune response of infants and children to disseminated infections with Neisseria meningitidis

Acute- and convalescent-phase sera from 34 children and 10 young adults were studied to determine if, at what age, and to which antigens of Neisseria meningitidis they respond during disseminated disease. Seven children older than two years of age who were infected with group C or Y strains developed significant increases in both binding and bactericidal antibody. Children infected with group B strains infrequently (eight [31%] of 26) had measurable increases in serum antibody to this capsular polysaccharide; response was meager when it did occur, was unrelated to age, and was considerably poorer than that of young adults, of whom 80% responded. Convalescent-phase sera from all children contained bactericidal antibody. Binding capacity for group B polysaccharide accounted for only 35% of the bactericidal activity in convalescent-phase sera of children infected with group B strains. Bactericidal antibody in the sera of children who did not respond to capsular polysaccharides was often to a lipooligosaccharide antigen.     

Human immunodeficiency virus isolation studies and antibody testing. Household contacts and sexual partners of persons with hemophilia

Virus isolation studies and human immunodeficiency virus (HIV) antibody testing were performed on 87 household contacts of 68 HIV antibody-positive hemophilic patients to determine the extent that HIV could be transmitted through heterosexual or through nonsexual, but intimate contact. Human immunodeficiency virus seropositivity was established for the 68 hemophiliacs by immunofluorescence method or enzyme-linked immunosorbent assay and confirmed by Western blot testing (for 66 patients). Fifty-one nonsexual contacts and 36 sexual partners of these hemophiliacs were tested for HIV antibody by immunofluorescence or enzyme-linked immunosorbent assay and Western blot. All sexual partners and all nonsexual household contacts were HIV antibody-negative, including six partners and nine parents of hemophiliacs from whom the virus had been isolated and seven parents and six partners of patients with AIDS. This study further demonstrates lack of transmission of HIV in intimate, but nonsexual settings, and suggests that heterosexual transmission, although well known to occur, may be relatively uncommon in hemophilic couples when the male and female partner have no other risk factors. It is hoped that intensive education and counseling programs will reduce exposure and maintain a low risk of heterosexual transmission.     

Usefulness of Transesophageal Echocardiography in Diagnosing and Guiding Correct Placement of a Right Ventricular Assist Device Malpositioned in the Left Atrium

In this report, we describe how transesophageal echocardiography was used not only to diagnose incorrect cannula position of a right ventricular assist device in the left atrium through a patent foramen ovale, but also to guide and to confirm correct cannula placement.     

Mitral valve prolapse

Mitral valve prolapse is a common valvular abnormality that is the most common cause of severe non-ischaemic mitral regurgitation in the USA. The overall prognosis of patients with mitral valve prolapse is excellent, but a small subset will develop serious complications, including infective endocarditis, sudden cardiac death, and severe mitral regurgitation. We present a comprehensive review of mitral valve prolapse, examining normal mitral anatomy, the clinical and echocardiographic features of mitral valve prolapse, and the pathophysiology and genetics of the disorder. We discuss the contemporary management of both asymptomatic and symptomatic prolapse, with particular attention to the timing and technique of surgical repair. We conclude that echocardiography is the method of choice for diagnosing mitral valve prolapse, that clinical and echocardiographic features can predict which patients with prolapse are at highest risk for complications, and that mitral valve repair is the treatment of choice for symptomatic prolapse.     

Phenotypic changes in MCF-7 cells during prolonged exposure to tamoxifen

MCF-7 breast tumor cells form multicellular nodules (foci) over a confluent monolayer in an estradiol (E2)-dependent, antiestrogen-sensitive reaction. A cell line cloned from MCF-7 that displays these phenotypes was probed to determine the effects of long term exposure to tamoxifen on the growth of foci, estrogen receptor alpha (ERalpha) status, and gene responsiveness to E2. In one of two experiments, a heterogeneous cell population emerged (TMX2) that over-expressed estrogen receptor alpha wild type mRNA (ERalpha mRNA) (approximately 20-fold) missing exon 3 (ERDelta3 mRNA) and its corresponding protein (ERDelta3P). On a per mRNA to protein basis, ERDelta3P and wild-type ERalpha were equivalently expressed. Return of the TMX2 population to medium without tamoxifen eventually selected for a population that expressed predominately wild-type ERalpha, whereas TMX2 clones over expressing ERDelta3 mRNA and ERDelta3P retained this phenotype in tamoxifen-free media. In both experiments, expression of all ERalpha mRNAs and proteins declined to barely detectable levels during 6-12 months exposure, concomitant with a progressive increase in the ability of the cells to form foci independently of E2 or tamoxifen. Selection for these various populations suggests that tamoxifen can induce and/or support certain cellular changes that lead to altered ERalpha expression, E2-independent cell growth and resistance to antiestrogens.     

Age-related changes in cardiac muscarinic receptors: decreased ability of the receptor to form a high affinity agonist binding state

Cardiac ventricular muscarinic cholinergic receptors and agonist binding properties were determined in Fischer 344 rats at 3, 12, and 24 months of age. Muscarinic receptors were determined by specific (-)-[3H]quinuclidinyl benzilate (QNB) binding, and the agonist binding properties were determined by competition assays. There were no differences in the concentration of the receptor or the dissociation constant of [3H]QNB binding among the three age groups. In cardiac membranes from 3- and 12-month-old animals, 5'-guanylyl-imidodiphosphate (Gpp(NH)p) increased by 16- to 18-fold (p less than .01) the concentration of carbachol required to inhibit [3H]QNB binding by 50% (IC50). At 24 months, however, Gpp(NH)p induced only a 2.7-fold shift in the carbachol IC50 value (p less than .01). The reduced shift was due to an increase in the carbachol IC50 value determined in the absence of Gpp(NH)p (p less than .01). There was no significant differences among the 3-, 12-, and 24-month-old animals in the half-maximal concentration of Gpp(NH)p required to produce the carbachol IC50 shift. The data indicated that with age there is a reduced ability of the muscarinic receptor to form a high affinity agonist binding state.