Induction of lymphocyte recruitment in the absence of a detectable immune response

Lymphocyte recruitment from blood into the lymph node is thought to be initiated by the presence of antigen. In this study, we have used lymphatic cannulation in sheep to demonstrate that the adjuvant ISCOMATRIX can induce dramatic lymph node activation in the absence of antigen. Consistent patterns of node shutdown (decreased output) and cell recruitment (increased output) with minimal blast cell responses were observed indicating that an antigen-specific immune response is not required. Production of IL-6, IL-8 and IFN-gamma, and the transient presence of red blood cells and neutrophils in the efferent lymph were associated with changes in efferent lymph cell trafficking. These early events may facilitate the screening of low frequency antigen-specific cells for binding to antigen and the subsequent amplification of the immune response.     

A processive versus a distributive mechanism of action correlates with differences in ability of normal and xeroderma pigmentosum group A endonucleases to incise damaged nucleosomal DNA

A DNA endonuclease, isolated from the nuclei of normal human and xeroderma pigmentosum complementation group A (XPA) cells, which recognizes predominately pyrimidine dimers, was examined for the mechanism by which it locates sites of damage on UVC-irradiated DNA. In reaction mixtures with low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease locate sites of UV damage on both naked and reconstituted nucleosomal DNA by different mechanisms. On both of these substrates, the normal endonuclease acts by a processive mechanism, meaning that it binds non-specifically to DNA and scans the DNA for sites of damage, whereas the XPA endonuclease acts by a distributive one, meaning that it randomly locates sites of damage on DNA. However, while both the normal and XPA endonucleases can incise UVC irradiated naked DNA, they differ in ability to incise damaged nucleosomal DNA. The normal endonuclease showed increased activity on UVC treated nucleosomal DNA compared with naked DNA, whereas the XPA endonuclease showed decreased activity on the damaged nucleosomal substrate. Since a processive mechanism of action is sensitive to the ionic strength of the micro-environment, the KCl concentration of the reaction was increased. At 70 mM KCI, the normal endonuclease switched to a distributive mechanism of action and its ability to incise damaged nucleosomal DNA also decreased. These studies show that there is a correlation between the ability of these endonucleases to act by a processive mechanism and their ability to incise damaged nucleosomal DNA; the normal endonuclease, which acts processively, can incise damaged nucleosomal DNA, whereas the XPA endonuclease, which acts distributively, is defective in ability to incise this substrate.      

A new amino acid mixture permits new approaches to the treatment of phenylketonuria

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.     

Doctors and patients in obstetrics and gynecology: the next 15 years.

The major impact on the development of obstetrics-gynecology during the next 15 years will come from the substantially increased number of of practicing physicians in the specialty and less rapidly increasing patient population they will serve. Even at present record low fertility rates, the annual number of births in the United States will increase slowly to a level near 4 million by the early 1980's; children already born will contribute to a 16 per cent increase in the female population 15 to 44 years of age between now and 1990. Over the same time interval, the number of practicing specialists will increase dramatically, based on rising numbers of medical school graduates and more Ob-Gyn residents; there will be a 52 per cent increase in certified specialists per unit population over the next 15 years.     

Periventricular astrocytosis and acute necrotizing encephalitis

Summary A group of rats presented with acute necrotizing encephalitis. The histopathological picture was the same in all the animals yet the periventricular regions where no morphologically appreciable signs of necrosis or infection could be found, presented with a florid astrocytic response. This periventricular astrocytosis was undetected with standard morphological methods but well-demonstrated with histoenzymatic techniques. It is presumed that these astrocytes originated in the ependyma with a possible cellular contribution from the choroid plexus.This work was done while in tenure of a Clinical Research Fellowship of the Medical Research Council (England) in the Royal Postgraduate Medical School, Lodon.