Late regrowth of pituitary adenomas after irradiation and/or surgery. Hazard function analysis

A retrospective analysis was performed on all patients with pituitary adenomas treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, St. Louis, Missouri. Of 210 patients treated from April 1954 through December 1982, 70 were treated with radiotherapy alone (RT), 121 received immediate postoperative RT (2 to 6 weeks), and 19 received RT following surgical failure. The mean follow-up time from the date of diagnosis for those patients alive at the time of last follow-up was 13.0 years (range, 3.0 to 30.0 years). Actuarial progression-free survival was analyzed up to 30 years. The 10-, 20-, and 30-year progression-free survival was 80.5%, 73.5%, and 73.5% for those patients treated with irradiation alone and 92.8%, 71.2%, and 44.0% for those treated with immediate postoperative irradiation. The median time to first failure from initial diagnosis by original treatment was 3.8 years for surgery alone, 4.2 years for RT only, and 10.2 years for surgery plus postoperative RT. Analysis for risk of recurrence per 5-year interval was performed using a hazard function analysis. The risk of recurrence after radiotherapy alone was greatest during the first 5-year interval after treatment and decreased to zero by 20 years. However, the risk of recurrence after primary surgery and postoperative radiotherapy revealed an increasing risk for recurrence up to 30 years after treatment. The concept of "cure" for pituitary adenomas requires extended follow-up.     

Platelet inhibitory effects of CRP preparations are due to a co-isolating low molecular weight factor.

We previously reported that C-reactive protein (CRP), an acute phase reactant, inhibits platelet activation through an effect upon a factor(s) critical to ADP-mediated secondary wave platelet aggregation but independent of a direct effect upon platelet contractile elements. However, a role for an accessory factor in this inhibitory effect became of concern because of an inconsistency in the effects of CRP preparations upon the platelet: inhibition was lost upon storage and CRP preparations differed, on a weight basis, in inhibitory capacity and sensitivity to the presence of the CRP ligand C-polysaccharide (CPS(. The studies presented herein were thus intended to assess whether an accessory factor was involved in the inhibition of platelet activation observed with CRP. We report that the activity of the inhibitory CRP preparations resulted from association with a low molecular weight factor (LMF) with an apparent nominal molecular weight of 8300-12,500 and an A280:A260 ratio of approximately 0.4. Purified CRP did not inhibit platelet responsiveness but CRP with associated LMF (CRP-LMF) did. Moreover, the inhibitory capacity of CRP-LMF but not LMF was substantially reversed in the presence of CPS. These studies indicate that the platelet inhibitory properties of CRP preparations result from and are contingent upon the presence of a co-isolating low molecular weight factor.     

Menstrual cycle and appetite control: implications for weight regulation

Hormonal fluctuations associated with the menstrual cycle influence appetite control and eating behaviour. Energy intake varies during the reproductive cycle in humans and animals, with a periovulatory nadir and a luteal phase peak. Patterns of macronutrient selection show less consistency but a number of studies report carbohydrate cravings in the premenstrual phase, particularly in women with premenstrual syndrome. The cyclical nature of food cravings are frequently, but not invariably, associated with depression. Fluctuations in appetite, cravings and energy intake during the menstrual cycle may occur in parallel with cyclical rhythms in serotonin, which can be accompanied by affective symptoms. The premenstrual phase can be considered as a time when women are especially vulnerable to overconsumption, food craving and depression; this is often associated with low serotonin activity.      

Defibrination with ancrod in experimental chronic immune complex nephritis

The role of fibrin deposition in experimental (crescentic) nephritis in rabbits, due to chronic immune complex deposition induced by BSA, has been studied. Fibrin deposition was prevented and in such animals crescent formation inhibited, suggesting that, as in experimental nephritis due to anti-GBM antibodies, fibrin deposition plays a major pathogenetic role in epithelial cell proliferation. However, in defibrinated animals, mesangial and endothelial cell proliferation, polymorpho-nuclear leucocyte infiltration and impairment of renal function could still occur. These studies are further evidence that defibrination may be of benefit in the treatment of rapidly progressive glomerulonephritis in man.     

Tolerance in TCR/Cognate Antigen Double-Transgenic Mice Mediated by Incomplete Thymic Deletion and Peripheral Receptor Downregulation

Influenza nucleoprotein (NP)-specific T-cell receptor transgenic mice (F5) were crossed with transgenic mice expressing the cognate antigenic protein under the control of the H- 2K^b promoter. Double-transgenic mice show negative selection of thymocytes at the CD4⁺8⁺TCR¹⁰ to CD4⁺8⁺TCR^hi transition stage. A few CD8 T cells, however, escape clonal deletion, and in the peripheral lymphoid organs of these mice, they exhibit low levels of the transgenic receptor and upregulated levels of the CD44 memory marker. Such cells do not proliferate upon exposure to antigen stimulation in vivo or ex vivo, however, they can develop low but detectable levels of antigen-specific cytotoxic function after stimulation in vitro in the presence of IL-2.     

Isolation of a DNA fragment which complements glutamine synthetase deficient strains ofS. pombe

Summary From a gene bank ofS. pombe DNA, a 5.6 kb clone was isolated which complemented mutants defective in glutamine synthetase (GS) activity. Sub-cloning fragments of this 5.6 kb clone showed that the complementing activity was localised in a 1.6 kb HindIII-Aval fragment and a partial DNA sequence revealed an open reading frame preceded by TATA sequences and a TGACTA sequence. Plasmid constructs carrying up to 3.4 kb of DNA used to transformgln ⁻ strains gave transformants which showed a wide range of GS activity, in some cases 100 times the wild-type level. These constructs identify DNA sequences lying downstream from the putative coding sequence which have effects on the total amount of enzyme activity, but do not affect the control imposed by the nitrogen source on which the cells are grown.     

Interaction of human plasma fibronectin with cariogenic and non-cariogenic oral streptococci

The interaction of purified human plasma fibronectin (Fn) with bacteria was studied with a variety of oral streptococci. Each of the strains of Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis, and Streptococcus mitis tested was aggregated by Fn to various degrees, depending on the concentration of Fn added to the test mixtures. Binding assays performed with radiolabeled Fn and various strains of streptococci demonstrated various capabilities to bind Fn, and the amount of Fn bound by each strain was paralleled by its Fn-induced aggregation, with S. mutans 6715 giving the highest values in both assays. Because of the avid binding of Fn by certain strains of potentially cariogenic streptococci, we investigated the possibility that Fn may be present in human saliva and may be adsorbed from saliva onto artificial tooth pellicles. Immunoreactive Fn was detected in paraffin-stimulated whole saliva by enzyme-linked immunosorbent assays of saliva adsorbed onto gelatin-coated cuvettes and by immunoelectroblots (Western blots) of salivary components separated on sodium dodecyl sulfate-polyacrylamide slab gels. Furthermore, immunoreactive Fn was found to be present in artificial tooth pellicles formed by incubating hydroxyapatite beads with whole human saliva. These results demonstrate that certain strains of oral streptococci bind to and are aggregated by Fn. The presence of Fn in artificial tooth pellicles suggests that this macromolecule may play a role in the attachment of potentially cariogenic and other oral streptococci to dental tissues.