Identification, purification and analysis of a 55 kDa lectin binding glycoprotein present in breast cancer tissue

The Helix pomatia agglutinin (HPA)-binding glycoproteins from primary breast cancers and their metastases were compared with appropriate normal control tissues on Western blots. From these studies a single glycoprotein of 55 kDa was found to bind HPA in tumours but not in normal control tissues. The glycoprotein was identified by protein sequencing as being homologous to human immunoglobulin heavy chain variable region. Subsequent immunostaining showed it to be immunoglobulin subclass A. IgA1 was purified from both tumour and normal tissue by affinity chromatography. It was demonstrated that IgA1 from tumour tissue bound HPA whereas IgA1 from normal tissue did not. The oligosaccharides were cleaved from the protein backbone and the glycans from the HPA-binding glycoform of IgA1 were compared with those from normal human IgA1. IgA1 from tumour tissue appears to be associated with an HPA-binding glycan which is not present on the normal tissue-derived IgA1.     

Lymphocyte response to silica among offspring of silicone breast implant recipients

The current study evaluated immune response to silicon dioxide in children born to women with silicone breast implants. In part one of the study, the T lymphocytes of 21 of 24 such children were significantly stimulated by silicon dioxide (silica). Part two consisted of eleven children, four born preimplantation and seven born postimplantation. None of the preimplant offspring showed T cell responses to silica; five of the seven postimplant children were positive for T cell memory for silica. Part three was a blinded study based on statistically significant differences in T cell stimulation with silicon dioxide between postimplant children and controls. These findings indicate a common immune reaction, that of T cell memory, occurs in mothers and their children born after exposure to silicone mammary implants placed prior to pregnancy. Since not all such children were breast fed the result favors transplacental passage of immunogens such as silicone oligomers or through maternofetal cellular traffic.     

Reduction and recovery of N-acetylglucosamine-1-phosphate transferase activity in the liver of sheep and rats after a single subcutaneous dose of tunicamycin

We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the human progesterone receptor (PGR) gene. This polymorphism will be a useful marker in the genetic study of disorders affecting female endocrine systems, such as progesterone resistance and breast, uterine, and ovarian cancers.     

The contribution of classical (beta1/2-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta3-adrenoceptor agonists of differing selectivities

The role of beta3- and other putative atypical beta-adrenoceptors in human white adipocytes and right atrial appendage has been investigated using CGP 12177 and novel phenylethanolamine and aryloxypropanolamine beta3-adrenoceptor (beta3AR) agonists with varying intrinsic activities and selectivities for human cloned betaAR subtypes. The ability to demonstrate beta1/2AR antagonist-insensitive (beta3 or other atypical betaAR-mediated) responses to CGP 12177 was critically dependent on the albumin batch used to prepare and incubate the adipocytes. Four aryloxypropanolamine selective beta3AR agonists (SB-226552, SB-229432, SB-236923, SB-246982) consistently elicited beta1/2AR antagonist-insensitive lipolysis. However, a phenylethanolamine (SB-220646) that was a selective full beta3AR agonist elicited full lipolytic and inotropic responses that were sensitive to beta1/2AR antagonism, despite it having very low efficacies at cloned beta1- and beta2ARs. A component of the response to another phenylethanolamine selective beta3AR agonist (SB-215691) was insensitive to beta1/2AR antagonism in some experiments. Because no [corrected] novel aryloxypropanolamine had a beta1/2AR antagonist-insensitive inotropic effect, these results establish more firmly that beta3ARs mediate lipolysis in human white adipocytes, and suggest that putative 'beta4ARs' mediate inotropic responses to CGP 12177. The results also illustrate the difficulty of predicting from studies on cloned betaARs which betaARs will mediate responses to agonists in tissues that have a high number of beta1- and beta2ARs or a low number of beta3ARs.     

Postoperative complications in proximal stomach resection

During 20 years (1972-1994) the authors carried out proximal resections of the stomach in 106 patients for cancer of proximal part of the stomach extended to the esophagus. Morphological verification data are presented. Total lethality rate made up 20.8%. It decreased with gaining of experience and improvement in selection of patients (1972-1982--29.6%, 1983-1994--17.7%). The most common complication in postoperative period was exudative pleuritis: in 16% of operated patients insufficiency of sutures of the esophagogastric anastomosis was observed. For prophylaxis of suture insufficiency pyloroplasty by Heineke-Mikulich and continuous (to 4-5 days) naso-gastral drainage were of principal significance. Great importance was attached to establishment of the anastomosis by the method developed by the authors. The results of the operations depend also on the operative approach: two-stage combined approach (laparotomy, thoracotomy) brings the least lethality.     

Detection of the local H+ gradients on the internal mitochondrial membrane

Respiration-dependent responses of a pH probe (fluorescein isothiocyanate, FITC), covalently bound to the membrane proteins of mitochondria and submitochondrial particles (SMP) have been studied. A spectral shift indicating FITC deprotonation was observed when respiration was activated in coupled mitochondria. Such a response was increased by valinomycin and reduced by uncoupler. Some FITC deprotonation was detected in the presence of excess of an uncoupler, but the response was smaller and insensitive to valinomycin. FITC deprotonation was also observed in submitochondrial particles after succinate addition. In this case it was not affected by uncoupler. Increase in the buffer concentration was found to (i) decrease the FITC response and (ii) increase the rate of uncoupled respiration in both mitochondria and submitochondrial particles. The results are consistent with the assumption that respiration initiates appearance of local H+ activity gradients on the inner side of the internal mitochondrial membrane during the steady-state H+ pumping. We suggest that the formation of this gradient is due to kinetic barrier to proton transfer from the bulk phase to the respiratory proton pump vicinity.     

Congenital erythrocytosis with elevated erythropoietin level: an incorrectly set "erythrostat"?

It is well documented that IL-6 plays a critical role in B cell terminal differentiation, and in mucosal sites it stimulates proliferation and large-scale secretion of immunoglobulin by B cells, especially those committed to IgA production. The close juxtaposition of IL-6 mRNA+ cells to plasma cells in the intestinal lamina propria supports the proposition that IL-6 production in situ is an important factor determining the outcome of antibody responses at that site. However, it has not been established previously whether exogenous IL-6 could boost antibody responses in the intestine if administered with a challenge antigen. Using a resected gut loop (Thiry-Vella loop) model, we have been able to demonstrate that in mice with double loops, antibody containing cell responses to lumenal administration of ovalbumin were 50% greater in loops given intralumenal recombinant IL-6 with the challenge antigen, than in loops challenged with antigen alone. This demonstrates the efficacy of IL-6 in promoting accumulation of antibody secreting cells in the gut, and suggests a potential therapeutic role for IL-6 to enhance responses to mucosal vaccines.