Study of the structural changes in irradiated erythrocyte membranes using 2,6-toluidinonaphthalene sulfonate

It was shown that 2,6-tolyidinonaphthalene sulfonate (2,6-TNS) is localized mainly at the bilayer-water border of the erythrocytic membranes. Under the effect of gamma-radiation the rearrangements occur in the membrane which bring about changes in the distribution of the probe between the membrane and the medium. The lifetime of the excited state of 2,6-TNS after irradiation varies slightly.     

Analysis of NAT2 point mutations with biological microchips

The NAT2 product, N-acetyltransferase 2, is involved in biotransformation and detoxification of several aromatic amines (in particular, 2-aminofluorene, 4-aminobiphenyl, and 4-naphthylamine), which are strongly mutagenic and carcinogenic, and acetylates some drugs, affecting their metabolism. A biological microchip was developed to detect 16 point mutations, which determine 36 alleles and 660 genotypes of NAT2. The genotypes can be divided into four groups according to the acetylator phenotype: groups with rapid (R/R), intermediate (R/S), or slow (S/S) acetylation and a group combining intermediate and slow alleles (“R/S or S/S”). The last group includes the alleles determined by combinations of seven mutations (191G/A, 282C/T, 341T/C, 481C/T, 590G/A, 803A/G, and 857G/A), whose cis or trans position is detectable by restriction enzyme analysis. The NAT2 genotype was unequivocally established for 37 out of 71 DNA specimens, while the other 34 specimens were characterized by more than two genotypes. By the acetylator phenotype, 16 out of the 34 genotypes were assigned to the group “R/S or S/S,” combining mutations 282C/T, 341T/C, 481C/T, 590G/A, and 803A/G. Thus, the biochip allows primary analysis of most NAT2 polymorphic substitutions, the acetylator genotype being important to know in predictive medicine and individualized therapy.     

Co-expression of the Thermotoga neapolitana aglB gene with an upstream 3'-coding fragment of the malG gene improves enzymatic characteristics of recombinant AglB cyclomaltodextrinase

A cluster of Thermotoga neapolitana genes participating in starch degradation includes the malG gene of sugar transport protein and the aglB gene of cyclomaltodextrinase. The start and stop codons of these genes share a common overlapping sequence, aTGAtg. Here, we compared properties of expression products of three different constructs with aglB from T. neapolitana. The first expression vector contained the aglB gene linked to an upstream 90-bp 3'-terminal region of the malG gene with the stop codon overlapping with the start codon of aglB. The second construct included the isolated coding sequence of aglB with two tandem potential start codons. The expression product of this construct in Escherichia coli had two tandem Met residues at its N terminus and was characterized by low thermostability and high tendency to aggregate. In contrast, co-expression of aglB and the 3'-terminal region of malG (the first construct) resulted in AglB with only one N-terminal Met residue and a much higher specific activity of cyclomaltodextrinase. Moreover, the enzyme expressed by such a construct was more thermostable and less prone to aggregation. The third construct was the same as the second one except that it contained only one ATG start codon. The product of its expression had kinetic and other properties similar to those of the enzyme with only one N-terminal Met residue.     

Association of <Emphasis Type="Italic">NAT2</Emphasis> polymorphisms with susceptibility to psoriasis in the Moscow population

N-acetyltransferase 2 (NAT2) is a key enzyme of biotransformation phase II that metabolizes genotoxic compounds such as carcinogens and mutagens in different types of cells. A decreased NAT2 activity may correlate with sensitivity to harmful environmental factors, thus increasing susceptibility to different multifactorial diseases, including dermatologic conditions like psoriasis. A biochip developed in our lab to detect 17 NAT2 SNPs was tested on 279 clinical DNA samples from 180 patients with psoriasis and 99 healthy individuals, all residents of Moscow. Six polymorphisms that are most common in European populations (282C > T, 341T > C, 481C > T, 590G > A, 803A > G, and 857G > A) were detected. The NAT2 allele and genotype frequencies for individual SNPs did not differ between patients and healthy individuals. The frequency of the slow acetylation phenotype was increased in patients with type II psoriasis and in normosthenic patients as compared to controls (OR = 1.76, P = 0.177 and OR = 2.07, P = 0.050, respectively). Genotype 341C/C,481T/T,803G/G was significantly more frequent in patients who smoked at least one pack of cigarettes per day and in those who regularly consumed alcohol than in controls (OR = 7.42, P = 0.008 and OR = 106.11, P = 0.003, respectively). The frequency of genotype 341T/T, 481C/C, 590A/-, 803A/A was increased in patients with adverse reactions to medications (OR = 2.05, P = 0.099). Thus, our data suggest that some NAT2 genotypes in combination with certain lifestyles can be considered risk factors of psoriasis in the Moscow population.     

Moderate alcohol consumption is associated with better endothelial function: a cross sectional study

Background

Natural heterologous valved conduits with a diameter greater than 22 mm that can be used for right ventricular outflow tract reconstruction in adults are not commercially available. The purpose of this study was to measure by ultrasonography the maximum diameter of the distended jugular veins of horses and cattle, respectively, to identify a population of animals that would be suitable for post-mortem collection of jugular veins at sizes greater than 22 mm.

Methods

The study population included 60 Warmblood horses, 25 Freiberger horses, 20 Brown Swiss cows, and 20 Holstein cows (including 10 Holstein and 10 Red Holstein). The maximum cross-sectional diameter of the distended jugular veins was measured at a location half-way between the mandibular angle and the thoracic inlet. The thoracic circumference (heart girth length) was used as a surrogate of body size. The jugular vein diameters of the different populations were compared by analysis of variance and the association between heart girth length and jugular vein diameter was determined in each of the four study populations by linear regression analysis.

Results

There was considerable individual variation of jugular vein diameters within each of the four study populations. There was no statistically significant relationship between thoracic circumference and jugular vein diameter in any of the populations. The jugular vein diameters of Brown Swiss cows were significantly larger than those of any of the other populations. Warmblood horses had significantly larger jugular vein diameters compared to Freiberger horses.

Conclusion

The results of this study suggest that the production of bovine or equine xenografts with diameters of greater than 22 mm would be feasible. Differences between species and breeds need to be considered. However, prediction of the jugular vein diameter based on breed and heart girth length in an individual animal is inaccurate.     

Diverse repertoire of the MHC class II-peptide complexes is required for presentation of viral superantigens

Among other features, peptides affect MHC class II molecules, causing changes in the binding of bacterial superantigens (b-Sag). Whether peptides can alter binding of viral superantigens (v-Sag) to MHC class II was not known. Here we addressed the question of whether mutations limiting the diversity of peptides bound by the MHC class II molecules influenced the presentation of v-Sag and, subsequently, the life cycle of the mouse mammary tumor virus (MMTV). T cells reactive to v-Sag were found in mice lacking DM molecules as well as in A(b)Ep-transgenic mice in which MHC class II binding grooves were predominantly occupied by an invariant chain fragment or Ealpha(52-68) peptide, respectively. APCs from the mutant mice failed to present v-Sag, as determined by the lack of Sag-specific T cell activation, Sag-induced T cell deletion, and by the aborted MMTV infection. In contrast, mice that express I-A(b) with a variety of bound peptides presented v-Sag and were susceptible to MMTV infection. Comparison of v-Sag and b-Sag presentation by the same mutant cells suggested that presentation of v-Sag had requirements similar to that for presentation of toxic shock syndrome toxin-1. Thus, MHC class II peptide repertoire is critical for recognition of v-Sag by the T cells and affects the outcome of infection with a retrovirus.     

An unusual presentation of a malignant jejunal tumor and a different management strategy

BACKGROUND: Malignant small bowel tumors are very rare and leiomyosarcoma accounts for less than 15% of the cases. Management of these tumors is challenging in view of nonspecific symptoms, unusual presentation and high incidence of metastasis. In this case report, an unusual presentation of jejunal sarcoma and management of liver metastasis with radiofrequency ablation (RFA) is discussed. CASE PRESENTATION: A 45-year-old male presented with anemia and features of small bowel obstruction. Operative findings revealed a mass lesion in jejunum with intussusception of proximal loop. Resection of bowel mass was performed. Histopathological findings were suggestive of leiomyosarcoma. After 3-years of follow-up, the patient developed recurrence in infracolic omentum and a liver metastasis. The omental mass was resected and liver lesion was managed with radiofrequency ablation. CONCLUSION: Jejunal leiomyosarcoma is a rare variety of malignant small bowel tumor and a clinical presentation with intussusception is unusual. We suggest that an aggressive management approach using a combination of surgery and a newer technique like RFA can be attempted in patients with limited metastatic spread to liver to prolong the long-term survival in a subset of patients.     

Stages in the improvement of drug therapy at a polyclinic]

Within 1968-1997 the authors studied the steps of introduction of the achievements of the medical science, technology and pharmacology to therapy of exacerbations and complications of peptic ulcer (PU). The scientific and practical value of endoscopic, histological, biochemical and bacteriological examinations in the improvement of the methods of pharmacotherapy of exacerbations and complications of PU was shown. Three phases of the PU development were indicated by the clinical signs and results of esophagogastroduodenoscopy, target biopsy and histological examinations. These data and available scientific achievements were assumed as a basis for the design of optimal drug combinations and their introduction to the medical practice. The use of such combinations made it possible to prevent relapses and life-threatening complications of the disease in the overwhelming majority of the patients. The best results of the pharmacotherapy were recorded in the years (1988-1997) when the drug combinations began to be used. The combinations provided eradication of Helicobacter pylori in the gastroduodenal mucosa and it was proved that in all the patients with PU and the relapsing lesions in the duodenum and in the overwhelming majority of the patients with gastric ulcer the disease developed at the background of chronic active gastroduodenitis associated with H.pylori. The success of the pharmacotherapy in the patients with PU was due to the use of the rational combinations of antibacterial and antisecretory agents.     

Work with youth--the basis of educational programs aimed at the prevention of HIV infection

During the recent 10 years, 1987-1997, syphilis morbidity was found to increase 60-fold in Omsk Province. In 1997 adolescents constituted 6.0% in the structure of persons who contacted the disease. In this year more than 500 adolescent using drugs were registered in the region. The introduction of drugs by injection was practiced by 9.6% of the adolescents. The program aimed mainly at changing the behavior of young people with orientation on the choice of a healthy mode of life and theirs information about risk factors associated with sex transmitted diseases particularly HIV infection is discussed.