Expression analysis of genes involved in apoptosis, proliferation and endoplasmic reticulum stress in ionomycin/PMA treated Jurkat cells.

PURPOSE: Activation of T cells by direct stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin (Io) results in numerous downstream signals that activate pathways enabling T cells to proliferate and produce cytokines. Inducible T cell activation is regulated predominantly at the transcriptional level. Therefore, we were interested to analyze the transcriptional activity of the 19 genes involved in the regulation of several important cellular processes. METHODS: Quantitative real-time (RT) PCR analysis was performed using mRNA-specific primers and SybrGreen for relative mRNA expression levels of all the examined genes. RESULTS: Our results showed c-kit expression in Jurkat cells, further confirmed by sequencing of c-kit mRNAspecific PCR product. The expected increased expression of interleukin (IL)-2 mRNA, together with moderate Ki-67 upregulation, indicate the proliferation of PMA/Io treated Jurkat cells. Significant upregulation of nuclear factor (NF)-κB, JNK and the prosurvival Bcl-2 was followed by activation of only one protein kinase RNA-like endoplasmic reticulum kinase (PERK) out of 3 main endoplasmic reticulum (ER) stress subpathways (ATF6 and spliced XBP were downregulated). NF-κB and JNK activation, as well as ERK downregulation were reactive oxygen species (ROS)-independent, shown by the lack of activation of antioxidative enzymes (SOD, NOS, GSTP1, gGCS and GR). C-kit was downregulated in the absence of exogenous SCF (c-kit ligand). CONCLUSION: Based on these data it is concluded that the PMA/Io treatment of Jurkat cells induced increased expression of IL-2, followed by upregulation of prosurvival genes belonging to the Bcl-2 family. Neither c-kit nor the antioxidative system were activated, excluding their role in Jurkat T-cell activation in the absence of exogenous c-kit ligand SCF.

Ethical and legal aspects of oncogenomics.

The discovery of the genes and cellular pathways that play fundamental roles in several diseases, and the understanding of many diseases at a molecular level due to the advances in the field of genomics, have revolutionized the diagnosis, therapy and prevention of human diseases. Application of genetic testing in numerous medical fields, including pharmacogenomics and oncogenomics, raised numerous ethical questions and introduced legal instruments that are aimed at ensuring the appropriate protection of human research participants. For the effective development of human genomics and translation of novel, validated biomarkers into potentially useful clinical applications in personalized medicine, there is a need for clear ethical standards and principles in all phases of clinical research.

HELLP syndrome as a cause of unexpected rapid maternal death--a case report and review of the literature.

Unexpected rapid death after delivery due to HELLP syndrome (HS) may become the subject of a forensic expertise. Since this syndrome is rarely encountered in forensic pathology, our objective was to point to some specific findings which might present forensic aspects of HS. These include unexpectedness, suddenness and fulminant course of this syndrome, which may confuse physicians, and on the other hand these characteristics cast doubt on violent injury, diagnostic oversights or iatrogenic injuries. Absence of classical signs of preeclampsia and non-specific clinical symptoms cause considerable differential diagnostic problems leading to a diagnostic delay or initial wrong non-obstetric diagnosis. A definitive postmortem diagnosis of HS in questionable cases of maternal death and consecutive forensic expertise of suspected medical malpractice should be based on accepted laboratory criteria and characteristic histopathological alterations.

Occupational intoxication with carbon monoxide.

The most important safety measure for prevention of CO poisoning is the installation of automatic systems that signal high CO concentrations in the work environment. Public health measures that include stringent pollution control, introduction of low-cost CO monitors, and public education aimed at the high-risk population (e.g., new workers, drivers) should decrease the number of deaths from CO poisoning and should save productive years of life. Toxicity of CO is a consequence of tissue hypoxia created by the displacement of oxygen from hemoglobin and the subsequent impairment of oxygen release to the tissues. Early symptoms of CO intoxication are insidious and can resemble other diseases; physical examination may be unremarkable. For these reasons, many cases of CO poisoning are not readily recognized.

[Basic characteristics of bacterial meningitis in patients treated at the Clinic for Infectious Diseases in Novi Sad during a 2-year period]. / Osnovne karakteristuke bakterijskih meningitisa kod bolesnika lecenih na Klinici za infektivne bolesti u Novum Sadu tokum dve godine.

Although known for centuries, bacterial meningitis is a disease which still causes death and invalidity no matter there are modern diagnostic methods and therapeutic modalities. Our investigation included 45 patients treated for a purulent meningitis during a two-year period at the Clinic for Infectious Diseases in Novi Sad. Most patients suffered from meningococcal meningitis. The onset of the disease was sporadic, during winter and spring, and there were no contact cases. Most patients were 2-3 and 8-15 years of age. Patients with pneumococcal meningitis had the most serious clinical picture, course of the disease, laboratory results, as well as outcome of the disease.

[Characteristics of persons killed by firearms and examined at the Institute of Forensic Medicine in Novi Sad 1989-1993]. / Karakteristike usmrcenih vatrenim oruzjem pregledanih u Zavodu za sudsku medicinu Novi Sad u periodu 1989-1993.

Gunshot wounds present an actual medical problem today. This research deals with a group of deceased persons murdered by firearms examined at the Institute of Forensic Medicine Novi Sad during the period 1989 - 1993 (402 persons). The analysis included sex and age structure as well as forensic medical categories connected to characteristics of gunshot wounds and wounds by explosion. Out of the total number of examined persons murdered during the analyzed period 11.92% of cases were deadly injured by firearms. There is an evident increase of those who die by firearms. During the same period of time correlations among homicides, suicides and accidents changed in favor of homicides. The average increase of homicides in 1991, 1992 and 1993 was 61.28% in regard to the average values of the first two years of the 5-year period.