syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction

Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well.     

Effects of the synthetic proteinase inhibitor, FOY, on hypercoagulability after surgery for esophageal carcinoma

Hypercoagulability develops after surgery for esophageal carcinoma, and it related closely to postoperative complications. This study evaluated the effects of the synthetic proteinase inhibitor, Cabexate Mesilate (FOY), on this hypercoagulability. The subjects used were 25 patients with a mean age of 63 who had undergone surgery for esophageal carcinoma. Of these, eight patients (test group) received FOY (2,000 mg/day) for three to 23 days after surgery, but 17 (control group) did not. In the test group, FOY controlled aggregation and release of the platelets and minimized their exhaustion. FOY almost completely checked the abnormal increase in thrombin activity which might trigger the hypercoagulability. Also, FOY suppressed the fibrinolytic activity slightly. These results indicate that FOY is effective in controlling hypercoagulability after surgery for esophageal carcinoma and in suppressing activity of the proteinases that cause both blood coagulation and fibrinolysis.     

Clinical significance of autoantibodies against neutrophil cytoplasmic components in patients with renal disease

The diagnostic significance of anticytoplasmic autoantibodies (ANCA) was studied in 71 renal patients. The ANCA test was positive in 67% of patients with Wegener's granulomatosis (WG), in 35% of those with a simultaneous renal and respiratory tract disease but not diagnosed as WG and in 22% of patients with a renal disease associated with unspecific collagenosis/vasculitis. Among WG patients ANCA positivity clearly correlated with the presence of active renal disease. Interestingly, both ANCA-positive and -negative patients were encountered in the group with acute renal failure and acute extracapillary glomerulonephritis associated with diffuse pulmonary infiltrates. The diagnostic and clinical significance of the ANCA test in these cases remains for the present obscure. In the majority of the ANCA-positive renal patients with respiratory tract abnormalities, the antibodies showed diffuse cytoplasmic staining and were mostly of the IgG class, of both IgG and IgM classes in some cases and of IgG, IgM and IgA classes in 1 patient. In patients with unspecific vasculitis/collagenosis the level of ANCA was rather low, and the distribution of different isotypes resembled that of patients with respiratory symptoms. A certain isotype of ANCA or staining pattern did not mark out any clinicopathologic subgroup among the patients. Our findings indicate that the clinical picture of ANCA-positive patients varies considerably and the ANCA test may not be as specific a marker of WG as previously suggested.     

Outcome of frozen embryo replacement cycles following elective cryopreservation of all embryos in women at risk of developing ovarian hyperstimulation syndrome

Aim: Our aim was to compare the outcome in subsequent frozen embryo replacement cycles in four groups of patients who had elective cryopreservation of all their embryos because they were considered to be at increased risk of developing severe ovarian hyperstimulation syndrome. Design: Sixty-two (91%) of 68 IVF cycles (68 patients) in which elective cryopreservation of all embryos was performed were analyzed. All patients continued on the GnRH agonist, buserelin, after oocyte recovery until the onset of vaginal bleeding. Frozen embryo replacement occurred in a hormone replacement cycle that started either on day 3 of the withdrawal bleed (group I;N=15) or after serum estradiol levels had fallen to <100 pmol/L (group II;N=16). The other patients commenced a frozen embryo replacement cycle several months later in either a hormone replacement (group III;N=15) or a natural (group IV;N=16) cycle. Results: Two patients developed severe ovarian hyperstimulation syndrome. There were no significant differences among the four groups regarding demographic variables, the dose of hMG used, and the clinical outcome. There was a higher but not significantly different clinical pregnancy rate in group I (26.7%), compared to group II (12.5%), group III (13.3%), and group IV (18.8%). Conclusions: Several options exist for the timing and protocol used for frozen embryo replacement in patients who had elective cryopreservation for the prevention of ovarian hyperstimulation syndrome, none of which was found to be clearly superior in this observational report.Presented at the 1994 Annual Conference of the American Fertility Society.     

Correction of hypercholesterolemia and dyslipoproteinemia by plasmapheresis in patients with stenocardia resistant to drug therapy

Plasmapheresis was used to correct blood lipid composition in patients with angina at rest and angina of effort (functional classes 3-4). In addition to a drop in total cholesterol and triglycerides, cholesterol in low and very-low-density lipoproteins fell abruptly, while high-density-lipoprotein cholesterol, on the contrary, increased considerably. Clinical improvement of the patients was also recorded.     

Isolated leukemic choroidal relapse in a child with acute lymphoblastic leukemia one year off therapy, diagnosed through transvitreal retino-choroidal biopsy

A serous retinal detachment and choroidal hemorrhagic infiltration developed in a 17-year-old girl with acute lymphoblastic leukemia one year after cessation of therapy without concurrent bone marrow (BM) or central nervous system relapse. A choroidal biopsy through a sclerotomy with simultaneous release of subretinal fluid revealed no malignant cells. Accordingly, she was treated with prednisone, topical corticosteroid and atropine with normalisation of vision and clinical findings. Five months later the retinal detachment and choroidal infiltration recurred. In order to re-attach the retina once more and obtain a representative choroidal biopsy, a pars plana vitrectomy followed by a retinotomy with removal of subretinal tissue was done revealing leukemic infiltration of the choroid. Simultaneously a BM relapse was diagnosed.