In vivo effect of prothymosin-alpha 1 on humoral and cell-mediated immune responses in the young rat.

There is a large body of evidence for the role of thymosin peptides in immunogenesis and immunity. In this paper we report on the influence of prothymosin alpha 1 (ProT-alpha 1), a hormone-like peptide derived from the calf thymus, on humoral and cellular immune reactions in the rat. Young adults received intraperitoneal injections of ProT-alpha 1 in the periods before and after immunization with cellular and soluble antigens. ProT-alpha-treatment produced a dose-dependent increase of both humoral and cell-mediated immune responses. The thymus weight increased but not that of spleen. Treatment of nonimmunized rats with this polypeptide significantly elevated the number of CD4+ and decreased the number of CD8+ cells in the peripheral blood. The results suggest a potent immunostimulatory activity of ProT-alpha 1 and imply direct action of this polypeptide on T lymphocytes.     

Multiple karyotypic aberrations in a polymorphous variant of Waldenstr?m macroglobulinemia.

A 71-year-old woman presented with malaise, skin bruising, epistaxis, and gingival bleeding of recent and prompt onset. There was no adenopathy. The liver and spleen were not enlarged. Bone marrow aspirate showed a polymorphous infiltration with lymphocytes (22%), typical Marschalko plasma cells (16%), plasmacytoid lymphocytes (29%), lymphoblasts (8%), and immunoblasts (13%). The immunoblasts morphologically resembled lymphosarcoma cells with a frequent "clover-leaf" appearance. An IgM paraprotein concentration in serum was 38.5 g/L. The bone marrow histopathology confirmed the presence of heterogenous cell infiltration, with 30% of the population being comprised of lymphoblasts and immunoblasts. In order to differentiate a polymorphous variant of Waldenstr?m macroglobulinemia (WM) from the more common small cell lymphocytic lymphoma (SLL) in anaplastic metamorphosis, flow cytometric studies were performed on marrow specimens. A typically bright surface IgM (lambda) was demonstrated with a less bright CD38. Further immunophenotype was HLA-DR+, CD19+, CD20+ and CD10-, CD22-, T-Ag- and kappa light chain- expression. This corroborated the diagnosis of an extremely rare, polymorphous variant of WM. The marrow cytogenetics disclosed 50% (10/20) pathologic metaphases 48,X,dup(X)(p21p22),der(2), +5,del(6)(q11q21), +12,inv(16)(p13q22), del(17) (p12), and 50% normal metaphases. The patient was treated with a LOPP protocol. She failed to respond and died 5 months after the diagnosis with myocardial and renal insufficiency complicating a pronounced pancytopenia in the peripheral blood.     

pS2 in breast carcinoma: association with steroid hormone receptor status

AIMS AND BACKGROUND: Knowledge of the steroid hormone receptors has proved to be of significant value in breast cancer. In the present study the possible importance of estrogen-regulated pS2 protein was investigated. Our direct purpose was to answer the question whether the expression of pS2 may be a marker of functional heterogeneity with respect to the steroid hormone receptor status. METHODS AND STUDY DESIGN: The study included 152 patients with primary, operable, histologically confirmed breast carcinomas. Histology specimens were reviewed and classified according to type, nodal status, tumor size and grade. Steroid hormone receptors were assayed by biochemical methods according to the procedures recommended by the EORTC. pS2 protein measurement was performed in breast carcinoma cytosols using an immunoradiometric assay. The results were analyzed by non-parametric statistical methods. RESULTS: A statistically significant inverse correlation between pS2 protein expression and histological tumor grade was found. The expression of pS2 protein was confirmed to be correlated with steroid hormone receptor status. However, it is important to point out that in spite of these statistically significant findings there were no significant biological associations due to overlapping individual pS2 protein values. The baseline level of expression of pS2 protein was obtained in histological grade III carcinomas with a negative steroid hormone receptor status. It was shown that the distribution of carcinomas according to the baseline level of pS2 protein expression was heterogeneous among estrogen receptor-positive carcinomas, and strikingly homogeneous among estrogen and progesterone-negative carcinoma. CONCLUSION: Our study suggested that PR and pS2 protein may identify distinct subsets of estrogen receptor-positive breast carcinomas.     

Magnetic fields, brain and immunity: effect on humoral and cell-mediated immune responses.

Magnetic fields (MF) can influence biological systems in a wide range of animal species and humans. We report here on the influence of static MF, locally applied to the brain area, on immune system performances in the rat. In the first series of experiments two AKMA micromagnets (M) with the influx density of 600 Gauss were bilaterally implanted (with "N" polarity facing the cranial bones) and fixed to the skull posterior to the fronto-parietal suture (parietal brain exposure). Rats implanted with iron beads (I) and sham-operated (SO) rats served as controls. Animals were exposed to MF or I during different periods of time before and after immunization with several soluble or cellular antigens. We report here on the in vivo immunoregulating effects of centrally applied MF on plaque-forming cell (PFC) response, local hypersensitivity skin reactions and experimental allergic encephalomyelitis. The selective influence of MF applied to different brain regions on PFC response was evaluated, as well. For this purpose, two M were bilaterally implanted in the area of (a) frontal, (b) parietal and (c) occipital brain regions. Rats were under the influence of MF for 20 days before and 4 days after immunization with sheep red blood cells. Groups of nonimmunized rats were exposed for 14, 24 and 34 days to parietally implanted M or I, and the number of peripheral blood CD4+ and CD8+ cells determined by mouse anti-rat W3/25 and MRC OX 8 monoclonal antibodies. The results show an overall in vivo immunopotentiation of humoral and cell-mediated immune responses in rats exposed to MF. Furthermore, these immunomodulating effects of centrally applied MF depend on at least two basic parameters, time of exposure and brain region exposed. The highest immune performance was obtained after exposure of the occipital brain region for a total period of 24 days. The results provide further evidence of the complex interrelationship between the environment, the central nervous system and the immune system.     

Dental age estimation on Bosnian–Herzegovinian children aged 6–14 years: Evaluation of Chaillet's international maturity standards

BackgroundDental age estimation in children plays an important role in forensic dentistry. The most commonly used method for age estimation was developed by Demirjian in 1973 on a French–Canadian sample. It generally overestimates dental age in many populations. International maturity standards were formed to obtain a predicted age with more confidence when ethnic origin was not available.ObjectivesThe aim of this study was to evaluate the applicability of Chaillet's international scores in the dental age assessment on Bosnian Herzegovinian (BH) children.MethodsOrthopantomograms of 1772 children, 980 girls and 792 boys aged 6.04–14.90 years, were assessed using Chaillet's international maturity tables and curves. The dental ages for both genders were compared to the chronological ages through a paired t-test.ResultsMean overestimation using Chaillet's international maturity standards were 0.09 ± 0.83 for girls and 0.28 ± 0.90 for boys. The absolute accuracy of residuals between the dental and chronological age were 0.65 ± 0.52 years for girls (Median: 0.52 years) and 0.73 ± 0.60 years for boys (Median: 0.57 years).ConclusionThe Polynomial compound formula was recommended to predict dental age with more accuracy for results of international maturity standards on BH children.     

Detection of DNA mutations based on analysis of multiple wavelength excitation/emission fluorescence kinetics curves in real-time PCR

The key method for therapies of various cancer types could be the molecular-targeted therapy, based on individual gene profile for each patient. One of the main procedures used for genetic testing is the real-time polymerase chain reaction (real-time PCR).     

Circulating haemopoietic progenitor cells in primary and secondary myelofibrosis: relation to collagen and reticulin fibrosis

The relationship between the extent of bone marrow reticulin and collagen fibrosis and the concentration of granulocytic (CFU-GM), erythroid (BFU-E) and megakaryocyte (CFU-Mk) progenitor cells in the peripheral blood of patients with primary agnogenic myeloid metaplasia (AMM) and secondary myelofibrosis (sMF) has not been definitively correlated. We studied 23 patients with established diagnosis of AMM and 12 patients with sMF for the extent of reticulin and collagen bone marrow fibrosis and for the spontaneous colony (sCFU-GM, sBFU-E and sCFU-Mk) formation. The control group consisted of 11 healthy volunteers. Trephine biopsy of the posterior iliac crest was performed in all individuals studied to determine the type and degree of reticulin and collagen fibrosis. Gomori's silver impregnation technique was used. sCFU-GM, sBFU-E and sCFU-Mk colony formation was related positively to spleen size, the white blood cell counts and the degree of collagen fibrosis in AMM (p < 0.01). Stimulated CFU-GM were also significantly correlated with the degree of bone marrow reticulin and collagen fibrosis. There was no correlation between the extent of peripheral blood progenitor concentration and the degree of bone marrow reticulin or collagen fibrosis in sMF and in control individuals. In conclusion, the extent of bone marrow fibrosis is significantly correlated with the peripheral blood progenitor colony formation in AMM but not in sMF.     

Biological evaluation of selected 3,4‐dihydro‐2(1H)‐quinoxalinones and 3,4‐dihydro‐1,4‐benzoxazin‐2‐ones: Molecular docking study

In order to investigate new potential therapeutically active agents, we investigated the biological properties of two small libraries of quinoxalinones and 1,4‐benzoxazin‐2‐ones. The results obtained showed that compounds 5 , 9–11 have good cytotoxic activity against HeLa cells where the lowest IC₅₀ value (10.46 ± 0.82 μM/mL) was measured for compound 10 . Additionally, the most active compounds ( 5 , 9 – 11 ) showed much better selectivity for MRC‐5 cells (up to 17.4) compared to cisplatin. In vitro evaluation of the inhibition of the enzyme α‐glucosidase showed that compounds 10 and 11 exert significant inhibition of the enzyme at 52.54 ± 0.09 and 40.09 ± 0.49 μM, respectively. Competitive experiments with ethidium bromide (EB) indicated that all tested compounds have affinity to displace EB from the EB‐DNA complex through intercalation, suggesting good competition with EB (K_sv = (3.1 ± 0.2), (5.1 ± 0.1), (5.6 ± 0.2), and (6.3 ± 0.2) × 10³ M^?1). A molecular docking study was also performed to better understand the binding modes and to conclude the structure–activity relationships of the synthesized compounds.

     

Anti-CD20 Monoclonal Antibody (Rituximab) for Therapy of Mediastinal CD20-Positive Large B-Cell Non-Hodgkin Lymphoma with a Local Tumor Extension into the Lung of a 10-Year-Old Girl

Intravenous therapy with the anti-CD20 antibody Rituximab has been recently approved for the treatment of CD20 positive non-Hodgkin's lymphoma (NHL) in adults but not in children. The authors present the benefits of its application for mediastinal NHL CD 20+ with a local extension into the lung of a 10-year-old-girl. Receiving the chemotherapy according to study NHL-BFM-95 for high-risk lymphoma the girl did not reach complete remission. Before the last chemotherapy block was started, a computed tomography scan of the thorax showed residue in the right lung. Twenty-five days after the last chemotherapy she received Rituximab at a dose of 375 mg/m 2 by intravenous infusion once a week for a total of four doses without the adverse reactions. Complete remission was achieved. The patient was high risk with lung involvement of lymphoma suggesting a pure prognosis. The results suggest that Rituximab may improve the outcome in high-risk patients and appeared to be safe and effective in children also.     

Sagittal osteotomy of the patella after Morscher

The aim of this study was to present long-term results of sagittal osteotomy of the patella after Morscher. The study included 70 patients treated for patellar dysplasia with a postoperative follow-up from nine to 20 years. There were 59 females and 11 males with an average age of 21 years at the time of operation. Results were evaluated for the entire group of 70 patients and then presented separately for the 30 patients in whom sagittal osteotomy of the patella was performed as a single procedure and 40 patients in whom, in addition to sagittal osteotomy of the patella, medialisation and ventralisation or distalisation of the tibial tuberosity were also performed. The mean value of the Wiberg patellar angle was 112 degrees preoperatively and 140 degrees postoperatively. In the whole group of patients excellent results were obtained in 24 (35%), good results in 30 (42%), fair results in 13 (19%) and poor results in three (4%) patients. In 30 patients with sagittal osteotomy as a single operation excellent results were obtained in 13 (43%), good results in 14 (47%) and fair results in three (10%) patients, while in the 40 patients with sagittal osteotomy and additional surgical procedures, 11 (27%) were excellent, 16 (40%) good, ten (25%) fair and three (8%) had poor results. Sagittal osteotomy of the patella after Morscher is an enrichment of the spectrum of the secondary-causal and preventive procedures for the treatment of patello-femoral disorders.