Epidermal growth factor (EGF) and EGF receptor in hypospadias

Environmental oncology is a discipline concerned with studies of multi-aspect relationships between environment and living organisms exposed to the modifying influence of carcinogenic agents. It also deals with general biological regularities involved in neoplasm development as well as their prevention in different species including man, animals and plants. Various investigations conducted at the Laboratory and supported with Russian and foreign grants (1991-1996) are briefly discussed. Among them are biotesting environmental carcinogens (aminoanthraquinons, by-products of drinking water chlorination, development of new testing systems and objects of detection involved in identification of genotoxic substances (criteria for formation of short-term test batteries and evaluation of perspectives, methods and results), investigation of xenobiotic metabolic activation (enzyme imprinting in adult animals), search for anticarcinogens (classification of carcinogenesis inhibitors, development of testing systems for modifiers selection), and establishing environment-related regularities of tumor growth. Vistas in environmental oncology development are discussed.     

MRI-radiofrequency tissue tagging in patients with aortic insufficiency before and after operation

We examined the relation between language dominance and regional cerebral blood flow (rCBF) during the intracarotid amobarbital procedure (IAP). A previous report limited to three patients suggested that dominant rather than nondominant hemisphere IAP may have a differential effect on rCBF. Behavioral assessment during the IAP also suggests that dominant hemisphere injection results in a differential effect on memory and affective symptoms rather than nondominant injection. Thirteen patients were assessed using single-photon emission CT (SPECT) brain imaging during both left and right IAP. The SPECTs were coregistered with the individual's MRI. Changes in rCBF during each IAP were compared with the patient's baseline SPECT. Nine patients had left hemisphere dominance, two were right dominant, and two had bilateral speech representation. In the left dominant subjects, left-hemisphere injection had a consistently greater effect on rCBF than right-hemisphere injection in the anterior (p < 0.005) and posterior (p < 0.01) temporal neocortex. There was also a trend for greater hypoperfusion in the frontal lobe of the left hemisphere. rCBF in the ipsilateral hippocampus was not significantly different after each injection (p > 0.05). In the two patients with right hemisphere speech, the reverse pattern was seen, with greater hypoperfusion after right (dominant) hemisphere injection. There was no consistent asymmetry in the two patients with bilateral speech. Dominant hemisphere IAP results in significantly greater hypoperfusion than does nondominant injection. These data provide a physiologic basis for behavioral differences noted after dominant versus nondominant IAP.     

The ori of filamentous phage phi Lf is located within the gene encoding the replication initiation protein

Because elevated intracellular cAMP suppresses T cell receptor (TCR)-mediated effector activity and/or proliferation in response to antigen but does not always affect IL-2-stimulated proliferation, the effects of cAMP on a T lymphocyte response to antigen resemble antigen-induced anergy. To test the hypothesis that elevated cAMP induces anergy in T lymphocytes, we have precultured murine Th1 clones responsive to porcine myelin basic protein (PMBP) with dibutyryl cyclic AMP (dbcAMP) or forskolin and subsequently removed the dbcAMP or forskolin and measured the proliferative response of the clones to antigen and antigen-presenting cells (APC) in the presence or absence of exogenously added interleukin-2 (IL-2). Cells precultured with dbcAMP or forskolin for 3 days did not proliferate or produce IL-2 in response to antigen and APC, but did proliferate to antigen and APC in the presence of IL-2. Cells that had not been stimulated recently with antigen/APC or IL-2 were not affected by dbcAMP, while cells stimulated recently with antigen/APC and IL-2 were susceptible to the anergizing effect of dbcAMP. These observations support the hypothesis that elevation in intracellular cAMP in antigen-activated Th1 clones, prior to subsequent culture with antigen, induces a state of anergy.     

Effect of flosequinan on human small subcutaneous arteries

We have investigated the effect of the novel hypotensive agent, flosequinan, on human small artery constrictor function. Concentration-dependent tension development to both noradrenaline and K+ was reduced in the presence of flosequinan. Arteries pre-contracted with noradrenaline demonstrated a greater concentration-dependent relaxation to flosequinan than did those pre-contracted with K+. Flosequinan depressed the sensitivity to extracellular Ca2+ of arteries pre-contracted with noradrenaline, but this effect was less marked in arteries pre-contracted with K+. These data support previous studies which suggest that flosequinan may affect receptor-mediated contraction by reducing Ca2+ sensitivity.     

Two native plasmids of Pseudomonas syringae pathovar tomato strain PT23 share a large amount of repeated DNA, including replication sequences

Strain PT23 of Pseudomonas syringae pv. tomato contains four native plasmids, designated A, B, C, and D. By DNA hybridization of genomic and plasmid DNA digests from the wild type and a plasmid-cured strain, we determined that c. 61 kb (c. 74%) of pPT23B is repeated in pPT23 A and only c. 17 kb (c. 21%) is in single copy in strain PT23. pPT23B also contains DNA repeated in the chromosome that occurs in three DNA fragments of 0.6, 4.6, and 9.6 kb that might be transposable elements. Additionally, the 9.6 kb fragment also shares sequences with the three other plasmids of strain PT23. By DNA hybridization with the origin of replication from a native plasmid of P. syringae pv. syringae and in vivo replication tests, we identified the origins of replication of plasmids A, B, and D and showed that they cross-hybridize. The putative par region from pPT23 A has also been identified and is not conserved in the other three native plasmids from strain PT23. By using the defined minimal origin of replication from pPT23 A as a probe, we showed that it is highly conserved in 14 strains belonging to nine different pathovars of P. syringae and that as many as five different native plasmids with closely related origins of replication coexist in the same cell. The duplication and reorganization of plasmids might therefore occur at high frequency and could be responsible for the existence of large numbers of native plasmids in P. syringae strains.     

Postpericardiotomy syndrome in pediatric heart transplant recipients. Immunologic characteristics

Clinical features of postpericardiotomy syndrome (PPS) occur in pediatric heart transplant recipients despite immunosuppression, which raises questions about the mechanism of PPS. We studied the clinical and immunologic characteristics of 15 pediatric heart transplant patients, ages 1.1 to 17.8 years (mean, 7.5 years); 7 had clinical evidence of PPS (PPS+), and 8 were without clinical features of PPS (PPS-). Indicators of PPS included fever, irritability, pericardial friction rub, leukocytosis without other cause, and pericardial effusion. The onset of PPS was from 9 to 26 postoperative days (mean, 16 days). Immunosuppressive regimens were comparable up to the day of PPS diagnosis in PPS+ patients, and up to day 16 in PPS- patients (average onset of PPS in PPS+ patients). No differences were found between groups with respect to weight-adjusted dosages of cyclosporin A, azathioprine, or corticosteroids. Mean cyclosporin A levels in PPS+ and PPS- patients were 142 +/- 88 ng/mL (mean +/- standard deviation) and 265 +/- 122 ng/mL (p = 0.045), respectively. Echocardiographic data on 3 PPS+ patients within 1 day of PPS diagnosis revealed pericardial effusions ranging from 5 to 24 mm. No data were available on the remaining 4 PPS+ patients. Minimal pericardial effusions (< 10 mm) were seen in 4 PPS- patients during a comparable time period. One PPS- patient required pericardiocentesis. Endomyocardial biopsy rejection grade did not differ between groups. Means pretransplant soluble interleukin-2 receptor levels did not differ between PPS+ and PPS- patients (758 +/- 410 vs 653 +/- 270 IU/mL); nor did the PPS+ pretransplant levels differ from levels obtained 1 or 2 months postoperatively (700 +/- 437 and 751 +/- 367 IU/mL, respectively). Although pretransplant percentages of the standard T-cell (CD2, CD3, CD4, CD8) and B-cell (DR and CD19) markers differed from post-transplant values, the changes could be explained by the immunosuppressive regimen and did not differ between PPS+ and PPS- patients. In the PPS+ patients, however, there were significant increases in the proportion of activated helper T cells (CD4+/25+) and cytotoxic T cells (Leu-7+/CD8+) following heart transplantation in comparison with pretransplant levels. We speculate that these changes in activation marker in PPS+ patients suggest a possible role for cell-mediated immunity in the pathogenesis of PPS in this group of patients.     

Electrochemical nitric oxide and nitrogen dioxide analyzer for use with inhaled nitric oxide

The use of inhaled nitric oxide (NO) in research and clinical applications requires the monitoring of NO and its autooxidation product nitrogen dioxide (NO2) in inspired gas and in the ambient environment. We describe an inexpensive electrochemical NO and NO2 analyzer that uses a critical orifice constant-flow controller and a microprocessor crossover correction for the measurement of NO and NO2 in the concentration range relevant to the use of inhaled NO. The analyzer proved to have good accuracy and precision for NO and NO2 in the range of concentrations relevant to studies of inhaled NO. In this range, the performance was similar to that of a chemiluminescence analyzer, and the response characteristics were not affected by varying the O2 concentration of the mixtures analyzed.     

Sperm auto - antibodies and anti-nuclear antigen antibodies in chronic dioxin - exposed veterans

The authors studied anti-nuclear antibodies (ANA) in 25 chronic dioxin - exposed veterans by IIF technics with Hep-2 cell line and sperm autoantibodies by agglutination test of Franklin-Dukes. The site of antibody binding on spermatozoon is detected by IIF test. The control group for ANA detection is 63 healthy persons of the same age as that of dioxin - exposed veterans and the control group for sperm autoantibodies is 36 healthy males of 28-63 years old, having 1-2 children. Obtained results show that the rate of ANA positive in veterans group is normal, and sperm auto-antibodies is also at normal range. The site of antibody binding on spermatozoon is predominantly head - head, rarely head - neck or tail - tail.