Does hybridoma technology still have a place in transfusion medicine?

Hybridoma technology has contributed to virtually all areas of biology and medicine and set the scene for important advances in cell biology and immunodiagnostics. Blood transfusion and transfusion medicine have benefited significantly from development in hybridoma technology, and this has resulted in the generation of a wide range of monoclonal antibodies to human blood group antigens. These antibodies have also had an impact on diagnostic techniques such as enzyme-linked immunosorbent assay and flow cytometry as well as on the application of therapeutic agents in the clinical environment. However, rapid advances in the development of knockout and transgenic mice as well as in nucleic acid-based immunization may well lead hybridoma technology into a new era.     

Influence of gene polymorphisms in adhesion molecules and inflammation mediators as risk factors for coronary heart disease and myocardial infarction--an overview

Cardiovascular diseases are influenced by inheritance and environmental factors. There is a growing number of genetic variants, which may be included in the genesis and development of coronary artery disease (CAD). CAD or ischemic heart disease is a set of clinical symptoms caused by inadequate transport of oxygen because of changes in coronary circulation leading to myocardial ischemia. The most common cause of CAD is atherosclerosis of coronary arteries, which primarily narrows or occludes the lumen of coronary arteries or stimulates thrombosis. In this review, the role of the most important polymorphisms in adhesion molecules, intracellular adhesion molecule-1, integrins alpha2beta1 and beta3, E-selectin as well as of inflammation mediators, tumor necrosis factors alpha and beta, in the development of CAD risk and myocardial infarction is discussed. A review of different genotyping results provides an insight into the mechanisms responsible for the disease risk and helps detect the key sets of predictive markers that are clinically informative.     

Delusional disorder of the paranoid type and unruptured intracerebral aneurysm--is there an association?

INTRODUCTION: Contrary to ruptured intracerebral aneurysm, according to our knowledge, not many papers have been published dealing with the relation of psychic/neuropsychological symptoms and unruptured intracerebral aneurysm (UIA). As to our knowledge, there is no published paper relating delusional disorder, paranoid type (DD-PT) and UIA, which can have important clinical implication. AIM, METHOD AND RESULTS: We describe a case of a woman who had DD-PT and UIA. The patient in her fifties, a typist with elementary school education, presented to the psychiatrist with the symptoms of irritability, insomnia, suspiciousness and paranoid ideas lasting for about a year. She showed clear symptoms of a delusional disorder. The psychiatrist established the diagnosis of DD-PT according to ICD-10. Olanzapine therapy, 10 mg day, was introduced immediately, causing partial improvement. In further diagnostic procedure, psychological tests were performed. The finding confirmed the diagnosis and average intellectual efficacy. The additional findings of impaired verbal fluency (VF) and hand tremor signalized an organic origin. The patient was referred to a neurologist, who assessed hand tremor, but otherwise the finding was normal. Brain CT revealed the possible UIA. Neurological hospitalization was quickly organized, and the definitive diagnosis of basilar artery aneurysm of 22 mm in diameter was made by angiography. Several days later, osteoplastic supraorbital craniotomy was performed at the neurosurgical department, with right sided keyhole approach in microsurgical technique, and the aneurysmal neck was clipped. The postoperative course was accompanied by meningitis treated with antibiotics. In neurological status, cerebellar symptomatology, tremor of the left hand, mild hemiparesis on the left side and the right eyelid ptosis persisted. Paranoid delusions were absent, but depressive symptoms emerged. Eight months after the surgery (approx. 11 months after the first test), control psychological testing was performed. The finding showed depression with significant perceptive disorganization. The VF result was within the normal limits. The patient is still being continuously followed-up. During preliminary diagnostic work-up, the possible organic cause and/or relation was suspected, based only on the psychiatric assessment and psychological report, because neurological status was free from any abnormalities other than tremor of the hands. CONCLUSION: The reported case confirmed the importance of detailed psychiatric interview and psychological testing in persons with psychic disorders, as well as the importance of multidisciplinary approach in the diagnosis and therapy. In this case, we could not find the exact way of connection between DD-PT and UIA.     

Psychological problems in children of war veterans with posttraumatic stress disorder in Bosnia and Herzegovina: cross-sectional study

Aim

To assess psychological problems in children as reported by their veteran fathers with war-related posttraumatic stress disorder (PTSD).

Method

The study group consisted of 154 veterans with war-related PTSD who were treated at the Mostar University Hospital. The control group consisted of 77 veterans without war-related PTSD who were selected from veteran associations by the snowball method. General Demographic Questionnaire, the first and fourth module of the Harvard Trauma Questionnaire–Bosnia and Herzegovina version, and the Questionnaire on Developmental, Emotional, and Behavioral Problems in Children, created specifically for the needs of this study, were used to collect data on veterans’ perception of psychological problems in their children.

Results

In comparison with veterans without PTSD, veterans with PTSD reported significantly more developmental (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.51-3.73), behavioral (OR, 3.92; 95% CI, 1.53-10.03), and emotional problems (OR, 17.74; 95% CI, 2.40-131.10) in their children.

Conclusion

Veterans with war-related PTSD more often reported developmental problems in their children. Father’s PTSD may have long-term and long-lasting consequences on the child’s personality.Posttraumatic stress disorder (PTSD) in one family member can negatively influence other family members and affect entire family dynamics (1-3). For many reasons, children in such families are especially vulnerable (4).Many studies have established that, in comparison with children of combat veterans without PTSD, the children of combat veterans with PTSD have more frequent and more serious developmental, behavioral, and emotional problems (2,5-10). Some of them also have specific psychiatric problems (11).Interviews with spouses and partners of combat veterans revealed that children of veterans with PTSD have more behavioral problems (5) and more frequent problems with authority, depression, anger, hyperactivity, and personal relationships (6-10) than children of veterans without PTSD. They are also more aggressive, use opiate drugs more often (6), and have learning difficulties and problems with diadic relations and emotional regulation (8). However, Harkness (8,12) did not find a significant association between the intensity of PTSD symptoms in veteran fathers and behavior of their children. On the other hand, it seems that the children of Vietnam War veterans did have behavioral problems, with veterans’ PTSD being a possible indirect factor in this association (13). It is assumed that direct war experience may disrupt the later capability of veterans to function as parents, leading to difficulties in the development and behavior of their children (12,13).With respect to the degree of individual and social traumatization caused by war trauma and post-war social situation in Bosnia and Herzegovina (BH), we assumed that war-related PTSD in veterans would have noticeable effect on the development of their children and that children of veterans with PTSD would have more psychological problems than children of veterans without PTSD.The aim of our study was to determine developmental, behavioral, and emotional problems of children in BH as reported by their veteran fathers with combat-related PTSD.     

Differential expression of leukocyte immunoglobulin-like receptors on cord-blood-derived human mast cell progenitors and mature mast cells

The leukocyte Ig-like receptors (LILRs) comprise a family of cell-surface immunoregulatory receptors with activating and inhibitory members. The inhibitory LILRs possess cytoplasmic ITIMs that down-regulate signaling by nonreceptor tyrosine kinase cascades. The activating members have a truncated cytoplasmic domain and signal through the FcR gamma chain. We examined the expression of LILRs on human mast cells during their development in vitro. Progenitor mast cells expressed cell surface inhibitory LILRB1, -B2, -B3, and -B4 and activating LILRA1. However, although mature cord blood-derived mast cells (hMCs) had detectable mRNA encoding multiple LILRs, none were expressed on the cell surface. Culture of progenitor mast cells or hMCs with various cytokine combinations failed to retain or induce cell surface expression of the LILRs. It is interesting that hMCs expressed LILRB5 in cytoplasmic granules and upon cross-linking of the high-affinity IgE receptor, released LILRB5 into the culture medium. Our results demonstrate that LILRs are developmentally regulated in human mast cells and that LILRB5 is expressed in mast cell granules and the release of soluble LILRB5 following IgE FcR-dependent stimulation, which has potential for amplification of mast cell-dependent, inflammatory responses.     

Assessment of toxicological profiles of the municipal wastewater effluents using chemical analyses and bioassays

The hazardous chemical contamination of untreated wastewater and secondary effluent from the wastewater treatment plant (WWTP) of the city of Zagreb, Croatia was comprehensively characterized using large-volume solid-phase extraction (SPE) and silica gel fractionation, followed by a detailed analysis of the resulting extracts by a combination of chemical and bioassay methods. Over 100 individual contaminants or closely related-contaminant groups were identified by high-resolution gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QTOF). Ecotoxicity profiling of the investigated samples, including cytotoxicity, chronic toxicity and EROD activity; inhibition of the multixenobiotic resistance (MXR), genotoxicicity and estrogenic potential, revealed the most significant contribution of toxic compounds to be present in polar fractions. Wastewater treatment using conventional activated sludge process reduced the initial toxicity of raw wastewater to various extents, ranging from 28% for algal toxicity to 73.2% for an estrogenic activity. The most efficient toxicity removal was observed for the polar compounds.     

Search for Klebsiella cell wall components cross-reactive with lymphocytes of B27+AS+ individuals

It has been suggested that some Klebsiella sp may cross-react with a cell surface determinant on the lymphocytes of B27⁺AS⁺ individuals. Studies were undertaken to identify the cross-reactive component of the Klebsiella and its relationship to a factor in Klebsiella culture filtrates capable of rendering the lymphocytes of B27-positive healthy controls susceptible to lysis by the anti-Klebsiella antiserum.Polyacrylamide gel electrophoresis of cell wall material of Klebsiella K43 prepared by sonication, high-speed centrifugation, and nonidet solubilization, demonstrated the presence of four major protein bands. When antisera raised in rabbits to each of these were tested for their cytotoxic effect on the lymphocytes of B27⁺AS⁺ individuals, an antiserum to one component only, of 40–52 K daltons molecular weight, reproduced the activity of the whole serum.Studies on the K43 filtrate indicated that the ‘modifying’ factor appeared to reside in a 25–50 K dalton component. Immunoelectrophoresis against anti-K43 serum demonstrated overlapping bands in the culture filtrate and the 40–52 K dalton cell wall fraction and these appeared to be identical on immunodiffusion. Antibody to the cell wall component removed both the ‘modifying’ activity and the appropriate protein band from the filtrate.The results suggest that a 40–52 K dalton component of the Klebsiella K43 cell wall is cross-reactive with a determinant on the lymphocytes of B27⁺AS⁺ individuals and is similar to or identical with a modifying factor in K43 culture filtrate which renders the lymphocytes of B27-positive healthy controls susceptible to lysis by anti-Klebsiella antiserum.