An anti-CD44 antibody does not enhance engraftment of DLA-identical marrow after low-dose total body irradiation

920 cGy total body irradiation (TBI) is adequate for consistently successful engraftment of marrow from dog leukocyte antigen (DLA)-identical littermates; however, the dose is inadequate to ensure a marrow graft from DLA-nonidentical unrelated donors. Such mismatched grafts are successful only after 1800 cGy, given in three fractions. While anti-T-cell reagents enhance engraftment of DLA-identical littermate marrow after 920 cGy, they fail to be effective in the DLA-nonidentical setting. However, a monoclonal antibody (mAb) to CD44, S5, was found to be very effective in enhancing engraftment of DLA-nonidentical marrow. The current study asked whether mAb S5 was also effective in the setting of DLA-identical littermate transplants. To this purpose, the TBI dose was lowered to 450 cGy, a dose after which 70% of such grafts failed. Four dogs were treated with antibody S5, 0.2 mg/kg on days −7 though −2 (per previously published protocol), given 450 cGy TBI followed by marrow grafts from their DLA-identical littermates. All four dogs rejected their grafts; two of these died from marrow aplasia, and two survived with endogenous marrow recovery. This result was not statistically significantly different from that in 17, historical (n = 5) and concurrent (n = 12), control dogs where 11 of 17 animals rejected. Even if ten experimental animals were transplanted and all six remaining dogs engrafted, the results still would not have been significantly different from control. This result is in contrast to the successful engraftment promoted by pretreatment with antibody S5 of DLA-nonidentical unrelated dogs, consistent with the notion that different host cells are involved in graft rejection in the two disparate histocompatibility settings.     

Serological diagnosis of HIV infection: incidence, outcome and significance of partial reactions found in western blot analysis.

Between May 1986 and April 1987 routine screening for anti-HIV antibody was performed by enzyme immunoassay (EIA) on 3344 serum samples. The 1160 samples found positive or borderline were further analysed in Western blot (Wb). We analysed the frequency of different patterns of 'intermediate' Wb reactions (1-3 'specific' bands) and tried to determine their significance by searching for possible modifications of the pattern of reaction a few months later. Of 1160 Wb, 461 were clearly positive, 489 negative and 210 'intermediate'. The latter consisted of: 92 sera with anti-p24 (associated or not), 23 with anti-gp 120 and 160, 16 with anti-p55, 12 with anti-p41, 10 with anti-p65, eight with anti-p17 and four with anti-p31. A non-specific pattern was observed in the remaining 45. Of these sera, 46% were obtained from high risk subjects, 38% from persons without risk and in 16% no reliable information was available. In 30 subjects (24 with p24 and 6 with p41), a second sample was obtained about three months later. The reaction persisted in nine, was replaced by another in five, and disappeared in 15. One subject with anti-p41 in the first sample became clearly positive. In one of the 15 samples with disappearance of the reaction, the antigen p24 was present as the only sign of HIV infection. Later samples of this subject showed clear seroconversion. In many subjects with and without risk of exposure to HIV, the Wb gives an intermediate pattern of reactions (1-3 specific bands), that does not permit definitive conclusion on one single sample. Later controls are therefore necessary. Most of these reactions do not correspond to HIV infection.     

Isolated coarctation of the aorta in the fetus: A diagnostic challenge

Isolated coarctation of the aorta (CoA) is estimated by the Centers for Disease Control and Prevention to account for 4%–6% of all congenital heart disease (CHD) in the United States, with a reported prevalence of ~4 per 10 000 live births. Prenatal recognition of coarctation is important as it may improve neonatal survival and reduce morbidity. However, despite advances in imaging and the trend toward detailed aortic arch assessment as part of a comprehensive fetal echocardiogram, isolated CoA may still elude prenatal detection, with potentially lethal consequences if the diagnosis is not suspected and the patent ductus arteriosus (PDA) closes spontaneously in postnatal life. The purpose of this review is to outline the methods of antenatal aortic arch evaluation in the current era, discuss “red flags” that raise the suspicion for CoA, including associated anomalies and serve as a repository of the most up to date information regarding its diagnosis in utero and its perinatal management. Other aortic arch abnormalities, such as interrupted aortic arch, or CoA associated with complex single ventricles, are not included in this review.     

Silver Doped Magnesium Ferrite Nanoparticles: Physico-Chemical Characterization and Antibacterial Activity

Spinel phases, with unique and outstanding physical properties, are attracting a great deal of interest in many fields. In particular, MgFe₂O₄, a partially inverted spinel phase, could find applications in medicine thanks to the remarkable antibacterial properties attributed to the generation of reactive oxygen species. In this paper, undoped and Ag-doped MgFe_2-xAg_xO₄ (x = 0.1 and 0.3) nanoparticles were prepared using microwave-assisted combustion and sol–gel methods. X-ray powder diffraction, with Rietveld structural refinements combined with micro-Raman spectroscopy, allowed to determine sample purity and the inversion degree of the spinel, passing from about 0.4 to 0.7 when Ag was introduced as dopant. The results are discussed in view of the antibacterial activity towards Escherichia coli and Staphylococcus aureus, representative strains of Gram-negative and Gram-positive bacteria. The sol–gel particles were more efficient towards the chosen bacteria, possibly thanks to the nanometric sizes of metallic silver, which were well distributed in the powders and in the spinel phase, with respect to microwave ones, that, however, acquired antibacterial activity after thermal treatment, probably due to the nucleation of hematite, itself displaying well-known antibacterial properties and which could synergistically act with silver and spinel.     

Inefficient killing of quiescent human epithelial cells by replicating adenoviruses: potential implications for their use as oncolytic agents

Cultured primary human cells have been widely used to assess the selectivity of oncolytic viruses as potential anticancer agents. As culture conditions can potentially have a significant impact on virus replication and ultimately cell killing, we evaluated the effects of dl309, a wild-type adenovirus, and dl01 / 07, a conditionally replicating adenovirus mutant, on quiescent and proliferating primary mammary epithelial cells. When primary cells were induced into quiescence, both viruses exhibited similar attenuated cell killing. However, cell killing by dl309 was superior to dl01 / 07 in proliferating primary cells. Analysis of viral effects at the level of entry, E2F activation, DNA replication, and late gene expression indicated that attenuation of dl309 in quiescent cells correlated with decreased expression of viral late genes such as hexon. In contrast, attenuation of dl01 / 07 in quiescent cells correlated with inefficient induction of E2F activity and inability to undergo efficient DNA replication. In proliferating cells, dl309 replicated efficiently, whereas dl01 / 07 still showed attenuated replication. In summary, our results indicate the intrinsic preference of wild-type adenoviruses for killing proliferating cells, which is an attractive feature for using adenoviruses as oncolytic agents. These results also highlight the need for the use of appropriate growth conditions for primary cells in vitro to distinguish subtle differences in cell killing among various oncolytic viruses.     

A C/T single nucleotide polymorphism at the tyrosine kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome

OBJECTIVE: To examine whether the insulin receptor (INSR) gene contributes to genetic susceptibility to the polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Academic endocrinology clinic. PATIENT(S): Ninety-nine women with PCOS as defined by the National Institutes of Health consensus and polycystic ovaries on ultrasonography, and 136 healthy controls. MAIN OUTCOME MEASURE: Frequency of genotypes of a single nucleotide polymorphism of the INSR gene in patients and controls. RESULT(S): After stratification of participants by body mass index, the frequency of the uncommon T allele of the INSR single nucleotide polymorphism was significantly increased in lean patients with PCOS (body mass index < or =27 kg/m2) compared with lean controls (relative risk, 2.1). CONCLUSION(S): The INSR gene is a susceptibility gene for PCOS among lean patients with PCOS. It remains to be determined whether the exon 17 C/T single nucleotide polymorphism is the susceptibility single nucleotide polymorphism for PCOS or whether it is in linkage disequilibrium with another INSR gene polymorphism.     

Fetal echocardiography: a window to the developing heart

This paper aims to help the reader understand the indications and the underlying physiologic concepts that relate to the findings obtained from a fetal cardiac evaluation. Techniques to obtain the basic fetal echocardiographic views and to identify gross cardiac abnormalities will also be discussed