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.     

Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes

The metabolism of amitriptyline was studied in vitro using cDNA-expressed human cytochrome P450 (CYP) enzymes 1A2, 3A4, 2C9, 2C19, 2D6 and 2E1. CYP 2C19 was the most important enzyme with regard to the demethylation of amitriptyline, the quantitatively most important metabolic pathway. CYP 1A2, 3A4, 2C9 and CYP 2D6 also participated in the demethylation of amitriptyline. CYP 2D6 was the sole enzyme mediating the hydroxylation of amitriptyline, and (E)-10-OH-amitriptyline was exclusively produced. CYP 2E1 did not metabolize amitriptyline. Concerning the quantitative relations, CYP 2C19 and 2D6 exhibited high affinities with Km values in the range of 5-13 mumol/l, whereas the affinities of 1A2, 3A4 and 2C9 were somewhat lower with Km values ranging from 74 to 92 mumol/l. CYP 2C19 displayed the highest reaction capacity per mole with Vmax equal to 475 mol h-1 (mol CYP)-1. The other enzymes had Vmax values in the range of 90-145 mol h-1 (mol CYP)-1. Allowing for the typical relative distribution of amounts of CYP enzymes in the liver, a simulation study suggested that, at therapeutic doses, on average about 60% of the metabolism depended on CYP 2C19. At toxic doses, CYP 2C19 is expected to be saturated, and CYP 3A4 may now play a dominant role in the metabolism.     

Anti-apoptotic signaling by a colony-stimulating factor-1 receptor/insulin receptor chimera with a juxtamembrane deletion

The intracellular mechanisms used by insulin and insulin-like growth factors to block programmed cell death are unknown. To identify receptor structures and signaling pathways essential for anti-apoptotic effects on cells, we have created a chimeric receptor (colony-stimulating factor-1 receptor/insulin receptor chimera (CSF1R/IR)) connecting the extracellular, ligand-binding domain of the colony-stimulating factor-1 (CSF-1) receptor to the transmembrane and cytoplasmic domains of the insulin receptor. Upon activation with CSF-1, the CSF1R/IR phosphorylates itself and intracellular substrates in a manner characteristic of normal insulin receptors. CSF-1 treatment protected cells expressing the CSF1R/IR from staurosporine-induced apoptosis. A chimeric receptor (CSF1R/IRDelta960) with a deletion of 12 amino acids from its juxtamembrane domain was constructed and expressed. CSF-1-treated cells expressing the CSF1R/IRDelta960 are unable to phosphorylate IRS-1 and Shc (Chaika, O. V., Chaika, N., Volle, D. J., Wilden, P. A. , Pirrucello, S. J., and Lewis, R. E. (1997) J. Biol. Chem. 272, 11968-11974). CSF-1 stimulated glucose uptake, mitogen-activated protein kinases, and IRS-1-associated phosphatidylinositol 3' kinase in cells expressing the CSF1R/IR but not in cells expressing the CSF1R/IRDelta960. Surprisingly, the CSF1R/IRDelta960 was as effective as the CSF1R/IR in mediating CSF-1 protection of cells from staurosporine-induced apoptosis. These observations indicate that the anti-apoptotic effects of the insulin receptor cytoplasmic domain can be mediated by signaling pathways distinct from those requiring IRS-1 and Shc.