B-type natriuretic peptide levels in adults with congenital heart disease and right ventricular failure

Right ventricular (RV) failure is a common problem for adults with systemic right ventricles or volume-overloaded right ventricles. The utility of B-type natriuretic peptide (BNP) levels for diagnosis and prognosis is now well documented in adults with acquired left ventricular (LV) systolic dysfunction, but not in the setting of RV failure. BNP levels were evaluated in adults with RV failure due to congenital heart disease and compared with levels in adults with acquired LV dysfunction and adults without structural heart disease.     

Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

Reactions of the subunits of the class II major histocompatibility complex molecule IAd.

Major histocompatibility complex (MHC) class II molecules are heterodimers formed by noncovalent linkage of alpha and beta chains. It has been shown that the subunits of the MHC class II molecules IAd and IEk bind antigenic peptides as well as antigenic peptides labeled with fluorescent probes. Laser scanning fluorescence microscopy on SDS/polyacrylamide gels demonstrates that the subunit-peptide complexes of IAd are stable over a wide pH range. Below pH 5.3 the heterodimer of IAd dissociates into the free chains, which still bind antigenic peptides such as the 18-amino acid peptide obtained by a tyrosine addition to a chicken ovalbumin peptide, Ova-(323-339)Y. The stability of preformed subunit complexes with fluorescein-labeled Ova-(323-339)Y was investigated by using high-performance size exclusion chromatography and epifluorescence microscopy. Each subunit forms a long-lived complex, both in detergent solutions and in reconstituted lipid bilayers. At 37 degrees C and pH 7.0 the dissociation half-time of the beta-subunit-peptide complex was determined to be 28 hr and that of the alpha-subunit-peptide complex was 10 hr. In contrast to the dissociation of the peptide from the IAd heterodimer, the half-times for dissociation of the peptide from the separate chains are not decreased at pH 5.0.     

Equilibration rates in lipid monolayers

A theoretical analysis is given for the rate of change of domain sizes in lipid monolayers at the air–water interface. The calculation is applicable to liquid domains formed from binary mixtures of lipids that form two coexisting liquid phases. Under conditions where the two lipid molecules have approximately equal areas, the equilibration rate does not involve macroscopic hydrodynamic flow in the subphase but rather depends on the diffusion coefficient of the lipid molecules. The calculation shows that the equilibration rate in binary mixtures of cholesterol and phosphatidylcholine is remarkably slow, the radius of a typical 20-μm diameter domain changing by as little as a part in a million per second. Under these circumstances, equilibration times of the order of days or weeks are expected. Even with such long times, the final state reached by the monolayer will in general be a state of metastable equilibrium, rather than true equilibrium.     

Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation

After bone marrow transplantation (BMT), a prolonged dysregulation of humoral immunity can be observed. In the present study, we investigated whether this is reflected in an abnormal production of specific antibodies (Ab) to the T-cell-dependent recall antigen tetanus-toxoid (TT). The study group consisted of children receiving transplants of an unmodified allogeneic graft and of adults receiving either a T-cell- depleted allogeneic or an unmodified autologous BM graft. Findings were compared with those in healthy controls. In pediatric graft recipients, who were routinely revaccinated early after BMT, the Ab response was quantitatively superior to that in adult graft recipients who did not receive early revaccination. In the majority of graft recipients, the time period after vaccination required to reach the peak level of antibodies was prolonged and the number of responding TT-specific B- cell clones was markedly decreased in comparison with controls. In controls, a low frequency of dominant B-cell clones may produce low quantities of homogeneous Ab components (H-Ab) against a heterogeneous background. However, in BM graft recipients, "overshooting" of Ab production by separate B-cell clones was observed, resulting in the development of H-Ab at a relatively high concentration. These abnormalities were present up to 10 years after BMT, irrespective of either the age of the recipient, the modulation of the graft, or the vaccination schedule used. It is hypothesized that the dysregulated Ab production is the consequence of activation of a restricted number of resting memory B cells, present in germinal centers, repopulating gradually after BMT. Our data show that routine revaccination early after BMT improves the humoral immune response. However, because of a clonally dysregulated Ab production, long-lasting qualitative defects may be present even after normalization of Ab titers.     

Noninvasive assessment of coronary vasodilation using magnetic resonance angiography

OBJECTIVES: The purpose of this study was to investigate the use of coronary magnetic resonance angiography (MRA) for assessing human epicardial coronary artery vasodilation. BACKGROUND: Coronary vasodilation plays a vital role in the human coronary circulation. Previous studies of epicardial coronary vasodilation have used invasive coronary angiography. Coronary MRA may provide an alternative noninvasive method to directly assess changes in coronary size. METHODS: Thirty-two subjects were studied: 12 patients (age 55 +/- 18 years) and 20 healthy subjects (age 34 +/- 4 years). High-resolution multi-slice spiral coronary MRA (in-plane resolution of 0.52 to 0.75 mm) was performed before and after sublingual nitroglycerin (NTG). Quantitative analysis of coronary vasodilation was performed on cross-sectional images of the right coronary artery (RCA). A time-course analysis of coronary vasodilation was performed in a subset of eight subjects for 30 min after NTG. Signal-to-noise ratio was also measured on the in-plane RCA images. RESULTS: Coronary MRA demonstrated a 23% increase in cross-sectional area after NTG (16.9 +/- 7.8 mm2 to 20.8 +/- 8.9 mm2, p <0.0001), with significant vasodilation between 3 and 15 min after NTG on time-course analysis. The MRA measurements had low interobserver variability (< or =5%) and good correlation with X-ray angiography (r=0.98). The magnitude of vasodilation correlated with baseline cross-sectional area (r=0.52, p=0.03) and age (r=0.40, p=0.019). Post-NTG images also demonstrated a 31% improvement in coronary signal-to-noise ratio (p = 0.002). CONCLUSIONS: Nitroglycerin-enhanced coronary MRA can noninvasively measure coronary artery vasodilation and is a promising noninvasive technique to study coronary vasomotor function.