Anti-U and haemolytic disease of the fetus and newborn

The red cell alloantibody, anti-U, is uncommon but is a recognised cause of haemolytic disease of the fetus and newborn. We describe six pregnancies complicated by the presence of maternal anti-U, and review nine other well-documented cases. In these 15 cases severe haemolytic disease occurred only with titres of > or = 1/512, and titres as high as 1/4000 were not necessarily associated with significant haemolysis. We recommend that an anti-U titre of > or = 1/128 or more at > or = 17 weeks of gestation is an indication for assessment of haemolysis in the fetus. Amniocentesis is the preferred initial investigation.     

beta-chemokines and neutralizing antibody titers correlate with sterilizing immunity generated in HIV-1 vaccinated macaques

One of the obstacles to AIDS vaccine development is the variability of HIV-1 within individuals and within infected populations, enabling viral escape from highly specific vaccine induced immune responses. An understanding of the different immune mechanisms capable of inhibiting HIV infection may be of benefit in the eventual design of vaccines effective against HIV-1 variants. To study this we first compared the immune responses induced in Rhesus monkeys by using two different immunization strategies based on the same vaccine strain of HIV-1. We then utilized a chimeric simian/HIV that expressed the envelope of a dual tropic HIV-1 escape variant isolated from a later time point from the same patient from which the vaccine strain was isolated. Upon challenge, one vaccine group was completely protected from infection, whereas all of the other vaccinees and controls became infected. Protected macaques developed highest titers of heterologous neutralizing antibodies, and consistently elevated HIV-1-specific T helper responses. Furthermore, only protected animals had markedly increased concentrations of RANTES, macrophage inflammatory proteins 1alpha and 1beta produced by circulating CD8(+) T cells. These results suggest that vaccine strategies that induce multiple effector mechanisms in concert with beta-chemokines may be desired in the generation of protective immune responses by HIV-1 vaccines.     

Prevalence of respiratory symptoms: marked differences within a small geographical area

BACKGROUND: Geographical differences in prevalence of respiratory symptoms have been reported between countries in the EC Respiratory Health Survey (ECRHS). The differences between two neighbouring centres in the Antwerp area were surprising. We therefore extended the screening phase of this study to four other areas with different features in this region. METHODS: Methods and questionnaires of the first phase of the ECRHS were used to estimate prevalence rates of respiratory symptoms in all areas. Information on some major personal and environmental risk factors was also obtained. RESULTS: Higher prevalence rates of both respiratory symptoms and personal risk factors were recorded in Urban Antwerp, Berendrecht-Zandvliet (harbour area) and Zwijndrecht (industrial area) than in Suburban Antwerp, Essen and Kasterlee (both rural). Neither personal nor environmental risk factors could provide satisfactory explanations for the area differences in symptoms. CONCLUSIONS: These large differences between groups of subjects living within a small geographical area prove that estimations of prevalence rates of a whole country based on measurements of prevalence in one specific area should be interpreted very cautiously. Epidemiological research within small geographical areas may thus still prove as informative as comparisons between countries for elucidating causes for different asthma prevalence.     

Presurgical profile preferences of patients and clinicians

BACKGROUND: Aortic regurgitation results from a pressure gradient across the aortic valve during left ventricular (LV) isovolumic relaxation, LV filling, and isovolumic contraction periods. Assuming the applicability of the simplified Bernoulli equation to this pressure-flow relation and constancy of aortic pressure during LV isovolumic relaxation and contraction periods, one can theoretically obtain estimates of the rates of LV isovolumic pressure fall and rise (deltaP/delta t) from the aortic regurgitation (AR) velocity signal. METHODS AND RESULTS: Mitral regurgitation (MR) and AR signals were recorded by using the continuous wave Doppler technique in 26 patients with combined mitral and aortic regurgitant lesions. The LV negative deltaP/delta t was obtained by dividing the time taken for the AR velocity to rise from 1 m/sec to 2.5 m/sec into 21 mm Hg, which is the estimated LV pressure drop between these points. In a similar fashion, the LV positive deltaP/delta t was obtained between 2.5 m/sec and 1 m/sec of the fast decelerating portion of the AR signal. The LV negative deltaP/delta t by the AR method ranged from 420 to 3500 mm Hg/sec and correlated well with that obtained by the MR method obtained in a blinded fashion (r = 0.95, p < 0.0001). The mean (SD) difference between the two methods was 30 (129) mm Hg/sec. Similarly, the LV positive deltaP/delta t by the AR method (range 420 to 2625 mm Hg/sec) correlated closely with that obtained by the MR method (r = 0.93, p < 0.0001), with the mean (SD) difference between the two methods being 38 (138) mm Hg/sec. CONCLUSIONS: Preliminary data presented in this study indicate the feasibility of obtaining a reliable estimate of LV positive and negative deltaP/delta t from the AR velocity profile. Thus the examination of the AR signal may give valuable insights into both LV systolic and diastolic functions.     

Characterization of a point mutation in the hormone binding domain of the estrogen receptor from an breast tumor

It is clear that growth of the MCF-7 breast cancer cell line is stimulated by estrogen and when estrogen is removed, growth slows. We have observed a tumor derived from MCF-7 cells that grows in athymic mice in the absence of estrogen stimulation. We hypothesized that a mutation in the estrogen receptor (ER) could be responsible for this constitutive growth. Using single stranded conformational polymorphism (SSCP) and DNA sequencing analysis, we have identified an ER containing a point mutation at position 415 (gly to val) within the hormone binding domain. The functional activity of this mutant was assessed in vitro and in vivo. Using transient transfection into an ER negative breast cancer cell with an ERE luciferase reporter gene, we found that both the wild-type and mutant receptors have similar efficacy. Additionally, the estrogenic responses were blocked by antiestrogens in a concentration related manner. We also found that tumors with the mutant receptor show similar growth response in athymic mice as wild-type: stimulation with estradiol and inhibition with antiestrogens. We conclude that the point mutation at position 415 (gly to val) is not responsible for constitutive growth.     

Materials research in Europe: Mapping excellence and looking ahead

The European Research Area has been established to coordinate national research policies and to encourage shared objectives, expertise, and resources throughout the European Union. To accomplish these goals, the European Research Area first needs knowledge of existing resources, fields of excellence, and potential for improvements as well as an idea of the direction of future research. This article describes the SMART project, established by the European Commission to identify important research topics for the future in the field of materials technology and to map materials research regions of excellence.     

Subcellular localization and cytotoxic activity of the GroEL-like protein isolated from Actinobacillus actinomycetemcomitans

The subcellular locations, ultrastructure, and cytotoxic activity of the GroEL-like protein from Actinobacillus actinomycetemcomitans were investigated. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) clearly indicated that synthesis of the GroEL-like protein is substantially increased after a thermal shock. Analysis of the purified native GroEL-like protein by transmission electron microscopy revealed the typical 14-mer cylindrical molecule, which had a diameter of about 12 nm. A. actinomycetemcomitans cells grown at 35 degreesC and heat shocked at 43 degreesC were fractionated, and fractions were separated by SDS-PAGE and analyzed by Western immunoblotting using antibodies to GroEL- and DnaK-like proteins. The GroEL-like protein was found in both the soluble and membrane fractions, whereas the DnaK-like protein was mostly found in the cytoplasm. An increase in specific proteins, including the GroEL- and DnaK-like proteins, was found in heat-shocked cells. The subcellular localization of the GroEL-like protein was examined by immunoelectron microscopy of whole cells. More GroEL-like protein was detected in stressed cells than in unstressed cells, and most of it was found not directly associated with outer membranes but rather in extracellular material. The native GroEL-like protein was assessed for cytotoxic activities. The GroEL-like protein increased the proliferation of periodontal ligament epithelial cells at concentrations between 0.4 and 1.0 microgram/ml. The number of cells in the culture decreased significantly at higher concentrations. A cell viability assay using HaCaT epithelial cells indicated that the GroEL-like protein was strongly toxic for the cells. These studies suggest the extracellular nature of the GroEL-like protein and its putative role in disease initiation.     

Insulin-like growth factor type 1--friend or foe?

OBJECTIVE: To emphasize that adrenal cysts are an uncommon finding and in most cases incidentally discovered during evaluation for nonspecific abdominal pain or even at outopsy. METHODS: We report a case of a non-hypers-creting right adrenal cyst in a middle-aged woman. RESULTS: A complete hormone, radiological and sometimes isotopic evaluation are required to make an accurate diagnosis and to determine the adequate treatment. CONCLUSION: Surgical resection is usually prompted by an inaccurate diagnosis and failed conservative treatments.     

The changes in the nervous structures under the chemical sympathectomy with guanethidine

The process of sympathectomy of white rats was achieved by injecting guanethidine intraperitoneally every day for 5.5 weeks at doses of 75 mg/kg of animal's weight. This process of sympathectomy was checked according to ganglion cervicothoracicum neurocytes state. The material was taken on days 1, 14, 30, 90 and 180 after cessation of guanethidine injections. It was ascertained that full sympathectomy under prolonged injections of high doses of guanethidine is reached at 5-6 months after the cessation of the injections, though pronounced total degeneration of gnl. stellatum neurocytes is marked on the 14th-30th days after cessation of the guanethidine injections. The following gradient of damaging influence of guanethidine was revealed: sympathetic gnl. cervicothoracicum neurocytes gnl. nodosum afferent neurocytes-neuromuscular synapsis skeletal muscle.     

Cranial bone flap fixation clamps: compatibility at MR imaging

To evaluate the compatibility of a commercially pure titanium aneurysm clip associated with magnetic resonance (MR) imaging at 1.5 T. Artifacts of the Spetzler titanium aneurysm clip were compared with those produced by six different nonferromagnetic aneurysm clips. With the titanium clip, no magnetic attraction was present, heating was minor, and the artifacts involved a small signal void. With the six other aneurysm clips, artifacts were larger. The presence of Spetzler titanium aneurysm clips is safe at MR imaging at 1.5 T or less.