Studies of bystander effects in human fibroblasts using a charged particle microbeam

PURPOSE: To determine the role of cell-to-cell mediated effects in the response of cells to different radiations by using a charged particle microbeam capable of targeting individual cells with counted particles. MATERIALS AND METHODS: Primary human fibroblasts were irradiated conventionally with X-rays or alpha-particles and scored for the induction of micronucleated or apoptotic cell formation at various times after irradiation. Cells were also individually irradiated with helium-3 particles from a microbeam and the distribution of damaged cells between hit and non-hit cells scored. RESULTS: Conventionally exposed fibroblasts showed a dose-dependent production of micronucleated and apoptotic cells 3 days after irradiation for both X-rays and alpha-particles, with a high RBE value for alpha-particles at low doses. Targeting individual alpha-particles, using a microbeam, to four cells within a population produced more micronucleated and apoptotic cells than expected on the basis of a direct effect only. CONCLUSIONS: This study provides direct evidence for the production of transmissible, cell-to-cell effects between hit and non-hit cells individually exposed to charged particles.     

Dopamine-dependent pathology and trace processes

During recent years, ceramide has received a lot of attention as a possible mediator of the cellular responses to a variety of apoptotic stimuli. In a manner analogous to generation of its sibling diacylglycerol, ceramide is generated by a phospholipase-C-type reaction from its lipid precursor sphingomyelin. Two observations led to the proposal that ceramide plays a role in apoptosis: (1) treatment of cells with tumor necrosis factor or other inducers of apoptosis leads to activation of sphingomyelinases and to an increase in cellular ceramide levels; (2) ectopic generation or administration of ceramide can mimic apoptotic cell death. Recently, several observations have challenged the notion that ceramide is an important cell-death mediator and have prompted a re-evaluation of previously published results.     

Combined use of left atrial transesophageal pacing and cordarone in atrial flutter

AIM: To investigate the effectiveness of superfrequent transesophageal left atrial stimulation (TLAS) and its combination with cordarone in management of atrial flutter (AF). MATERIALS AND METHODS: 650 patients with paroxysmal AF underwent TLAS. The paroxysm duration varied from 1 hour to 1 month. In 312 patients TLAS was performed prior to treatment with antiarrhythmic drugs (group 1), in 338 patients--after intravenous administration of cordarone (group 2). RESULTS: Superfrequent TLAS has restored sinus rhythm (SR) in 85(27.2%) and 169(50%) patients of groups 1 and 2, respectively (p < 0.001). TLAS promoted conversion of AF in atrial fibrillation (AFi) in 185(59.3%) and 159(47.1%) patients of groups 1 and 2, respectively (p < 0.01). Moreover, SR recovered 24-48 hours after TLAS in 87(27.9%) and 64(18.9%) patients of groups 1 and 2 respectively (p < 0.01). Sinus rhythm recovered in a total of 172(55.1%) and 233(69.0%) patients, AF was converted to AFi in a total of 88(31.4%) and 95(28.1%) patients (p > 0.05) of groups 1 and 2, respectively. TLAS was uneffective in 42(13.5%) and 10(2.9%) patients of groups 1 and 2, respectively. CONCLUSION: Superfrequent TLAS is a highly effective and non-invasive modality in the treatment of paroxysmal AF. It promotes recovery of SR. In some patients TLAS induces AFi which is more controllable by medication as regards the heart rate. Cordarone contributes to the response to TLAS in patients with paroxysmal AF.     

Inositol trisphosphate and cyclic ADP-ribose-mediated release of Ca2+ from single isolated pancreatic zymogen granules

In pancreatic acinar cells low (physiological) agonist concentrations evoke cytosolic Ca2+ spikes specifically in the apical secretory pole that contains a high density of secretory (zymogen) granules (ZGs). Inositol 1,4,5-trisphosphate (IP3) is believed to release Ca2+ from the endoplasmic reticulum, but we have now tested whether the Ca(2+)-releasing messengers IP3 and cyclic ADP-ribose (cADPr) can liberate Ca2+ from AGs. In experiments on single isolated ZGs, we show using confocal microscopy that IP3 and cADPr evoke a marked decrease in the free intragranular Ca2+ concentration. Using a novel high resolution method, we have measured changes in the Ca2+ concentration in the vicinity of an isolated AG and show that IP3 and cADPr cause rapid Ca2+ release from the granule, explaining the agonist-evoked cytosolic Ca2+ rise in the secretory pole.     

Thermodynamic stability of immunoglobulins and allosteric interactions with ferritin and protein A: distinct properties of the two antibodies of IgG2a subclass

The two anti-ferritin monoclonal antibodies of mouse IgG2a subclass, G10 and F11, are described that have similar affinity to human spleen ferritin and identical protein A-binding affinity. Antigen binding was shown to change significantly the protein A-binding parameters of the IgG2a antibodies. Antigen-induced conformational changes result in enhanced protein A-binding affinity of the G10 antibody while reduced affinity of the F11 antibody. Antigen binding does not change inherently low affinity of the anti-ferritin IgG1 antibody C5 to protein A. Differential scanning calorimetry revealed that the enthalpy and Gibbs free energy of denaturation for G10 was respectively by 19 and 29% higher than the corresponding parameters for F11. The lower structural energetics of F11 is associated with the lack of a calorimetrically revealed folding unit that may be responsible for distinct interaction between the antigen-binding and protein A-binding sites. This work provides experimental demonstration of the fact that functionally significant interactions between the two spatially remote recognition sites in antibodies of the same heavy chain isotype can be modulated by relatively small structural variations that also result in different thermodynamic stability.     

Study of antiinfectious potential of recombinant tumor necrosis factor-alpha

46 patients with coronary heart disease with hypercholesterolemia were exposed to therapeutic plasmapheresis (TP) in combination with alpha-tocopherol treatment (AT). The results of 3-month follow-up with assessment of the clinical status, lipid spectrum, lipid peroxidation, concentration of ceruloplasmin indicated high hypolipidemic effectiveness of TP 2-3 weeks after the treatment as shown by inhibition of lipid peroxidation and antioxidant system. The addition of AT prolonged the hypolipidemic effect of TP, promoted optimization of plasma antioxidant potential (a rise in HDL, stabilization of ceruloplasmin levels).     

Morphology of the lymphoid tissue of the bronchus in healthy persons of various ages, and the effect of smoking

The results of 315 endonasal operations on the lacrimal duct with long intubation are analyzed. The most incident complication of long intubation of the lacrimal duct is formation of intubation granulomas, which are most often localized in the inferior lacrimal canaliculus; their etiology is sometimes allergic--they form as a response of adjacent tissues to the material of the intubation tube, and the findings of our recent histological study prove it. The diagnosis of intubation granulomas is easy in the majority of cases. The treatment consists in removal and obligatory adequate total and local antiallergic therapy decelerating the growth and relapses of granulomas. After removal of the intubation tube the growth of granulations ceases and a fine cicatrix forms.     

The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301-302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301-302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301-302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301-302delAG deletion suggests that rather than being inherited from a common founder, the 301-302delAG may be a recurring mutation.     

The burn-resistant anti-autotoxic anti-immunocomplex serum

On the ground of studying of autotoxin and the organism autointoxication in burn the antiburn antiautotoxic antiimmunocomplexes serum was elaborated. The serum application provides all of the experimental animals survival while the thermal burn, mortal for the control.