Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

Oculo-facio-cardio-dental syndrome in three succeeding generations: genotypic data and phenotypic features

Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked disorder mainly manifesting in females. Patients show ocular, facial, cardiac, and dental abnormalities. OFCD syndrome is caused by heterozygous mutations in the BCOR gene, located in Xp11.4, encoding the BCL6 co-repressor. We report a Croatian family with four female members (grandmother, mother and monozygotic female twins) diagnosed with OFCD syndrome who carry the novel BCOR mutation c.4438C>T (p.R1480*). They present high intrafamilial phenotypic variability with special regard to cardiac defect and cataract that showed more severe disease expression in successive generations. Clinical and radiographic examination of the mother of the twins revealed a talon cusp involving the permanent maxillary right central incisor. This is the first known report of a talon cusp in OFCD syndrome with a novel mutation in the BCOR gene.

Oculo-facio-cardio-dental syndrome in three succeeding generations: genotypic data and phenotypic features.

Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked disorder mainly manifesting in females. Patients show ocular, facial, cardiac, and dental abnormalities. OFCD syndrome is caused by heterozygous mutations in the BCOR gene, located in Xp11.4, encoding the BCL6 co-repressor. We report a Croatian family with four female members (grandmother, mother and monozygotic female twins) diagnosed with OFCD syndrome who carry the novel BCOR mutation c.4438C>T (p.R1480*). They present high intrafamilial phenotypic variability with special regard to cardiac defect and cataract that showed more severe disease expression in successive generations. Clinical and radiographic examination of the mother of the twins revealed a talon cusp involving the permanent maxillary right central incisor. This is the first known report of a talon cusp in OFCD syndrome with a novel mutation in the BCOR gene.

131I-induced changes in rat thyroid gland function

Therapeutic doses of 131I administered to thyrotoxic patients may cause thyroid failure. The present study used a rat model to determine thyroid function after the administration of different doses of 131I (64-277 µCi). Thirty male Fisher rats in the experimental group and 30 in the control group (untreated) were followed for 6 months. The animals were 4 months old at the beginning of the experiment and were sacrificed at an age of 9 months. Hormone concentration was determined before 131I administration (4-month-old animals) and three times following 131I administration, when the animals were 7, 8, and 9 months old. The thyroid glands were removed and weighed, their volume was determined and histopathological examination was performed at the end of the experiment. Significant differences in serum triiodothyronine and thyroid-stimulating hormone concentration, measured at the age of 7, 8, and 9 months, were found in the experimental group. During aging of the animals, the concentration of thyroxin fell from 64.8 ± 8.16 to 55.0 ± 6.1 nM in the control group and from 69.4 ± 6.9 to 25.4 ± 3.2 nM in the experimental group. Thyroid gland volume and weight were significantly lower in the experimental than in the control group. Thyroid glands from the experimental group showed hyaline thickness of the blood vessel wall, necrotic follicles, a strong inflammatory reaction, and peeling of necrotic cells in the follicles. In conclusion, significant differences in hormone levels and histopathological findings indicated prolonged hypothyroidism after 131I administration to rats, which was not 131I dose dependent.

Effect of hyperbaric oxygenation on the regeneration of the liver after partial hepatectomy in rats

The aim of the present study was to assess the influence of hyperbaric oxygenation (HBO) on rat liver regeneration before and after partial hepatectomy. Rats were sacrificed 54 h after 15 percent hepatectomy, liver and body weights were measured, and serum alanine transaminase (ALT) and aspartate transaminase (AST) activity and albumin levels were determined. The lipid peroxide level, as indicated by malondialdehyde production in the remnant liver was measured, and liver sections were analyzed by light microscopy. Five groups of 10 rats in each group were studied. The preHBO and pre-hyperbaric pressure (preHB) groups were treated before partial hepatectomy with 100 percent O2 and 21 percent O2, respectively, at 202,650 pascals, daily for 3 days (45 min/day). The control group was not treated before partial hepatectomy and recovered under normal ambient conditions after the procedure. Groups postHBO and postHB were treated after partial hepatectomy with HBO and HB, respectively, three times (45 min/day). The preHBO group presented a significant increase in the initiation of the regeneration process of the liver 54 h postoperatively. The liver/body weight ratio was 0.0618 ± 0.0084 in the preHBO compared to 0.0517 ± 0016 g/g in the control animals (P = 0.016). In addition, the preHBO group showed significant better liver function (evaluated by the lowest serum ALT and AST activities, P = 0.002 and P = 0.008, respectively) and showed a significant decrease in serum albumin levels compared to control (P < 0.001). Liver lipid peroxide concentration was lowest in the preHBO group (P < 0.001 vs control and postHBO group) and light microscopy revealed that the composition of liver lobules in the preHBO group was the closest to normal histological features. These results suggest that HBO pretreatment was beneficial for rat liver regeneration after partial hepatectomy.

Expression of neutral glycosphingolipids in cytokine-stimulated human endothelial cells.

We compared immunohistochemical distribution of glycosphingolipids globotriosylceramide (GbOse(3)Cer) and globotetraosylceramide (GbOse(4)Cer) with that of E-selectin on human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor (TNF)-alpha. HUVECs activated by TNF-alpha were characterized by the highest expression of E-selectin and greatest adhesion of HL-60 cells as well compared to stimulation with interleukin-1beta or lipopolysaccharide. HUVECs activated by TNF-alpha also stained intensely with globoside antibodies, especially with the GbOse(3)Cer-directed one, staining being redistributed in a concentration-dependent manner. These results indicate the possible role of GbOse(3)Cer and GbOse(4)Cer in immune effector mechanisms of endothelium such as adhesion.

Reproductive ability of pubertal male and female rats

Ten Fisher rats 50 to 55 days of age made up the pubertal group, and ten rats 90 to 95 days of age served as the controls. The testicular and epididymal weights and volumes of the pubertal males were lower than those of the controls (P<0.001). There was also a difference in relative epididymal weight (P<0.001). The sperm of pubertal males was morphologically abnormal in 58.2 percent of cases, as opposed to only 3.8 percent in the controls (P<0.001). The mean number of spermatozoa in the control group was 11.9 I 10(6)/ml and their viability was 99.6 percent, while these values could not be determined for pubertal rats. Serum testosterone was higher in the pubertal animals than in the controls (2.52 ± 1.46 vs 0.92 ± 0.34 nM, P<0.01). The ovaries of control females were heavier than those of pubertal females (P<0.001) but there was no difference in their relative weights. Serum estradiol was similar in both groups (75.5 ± 12.8 vs 81.8 ± 14.7 nM, P>0.05). At the beginning of gestation, the pubertal dams weighed less than the controls (P<0.001) but following uterectomy the body weights were equal. Pubertal dams delivered fewer pups than the controls (8.1 ± 2.5 vs 10.4 ± 1.3, P<0.05). There was no difference in the body weights of their offspring or in the weights of their placentas. The results suggest that, in contrast to their female counterparts, pubertal male rats are not fully mature and have not reached complete reproductive capacity at 50-55 days of age

Behavioral characteristics of the offspring of adolescent rats

The aim of this study was to test the hypothesis that, during adulthood, the offspring of adolescent rats differ in emotionality, learning and memory from the offspring of adult rats. The behavior of the offspring of adolescent (age, 50-55 days) and adult rats (age, 90-95 days) was tested in the open field, activity cage, and passive and active avoidance apparatus. The latencies during training and testing in the passive avoidance apparatus of the offspring of adolescent parents were shorter than the latencies of control offspring (P<0.001 on both training and testing days). Offspring of adolescent parents showed shorter latency time in acquisition trials during active avoidance testing compared to control offspring (P<0.001). They also showed a higher number of active avoidance responses in the last four blocks of acquisition (P<0.001) and first two blocks of extinction trials (P<0.05 and P<0.001, respectively). The offspring of adolescent parents showed higher latency on the first day of testing in the open field (P<0.01) and a lower latency on the third day of testing (P<0.01). They also showed higher activity during all three days of testing (1st and 2nd day: P<0.01; 3rd day: P<0.05). The spontaneous activity of the offspring of adolescent parents in the activity cage was higher in the last three intervals of testing (P<0.001). In summary, the offspring of adolescent parents were less anxious and tended to be more active. The results of two learning and memory tests were opposite, but could be explained by a higher exploratory drive of the offspring of adolescent parents. This was probably due to chronic malnutrition stress and the disturbed mother-infant relationship in the litters of adolescent mothers

Bone marrow involvement and the prognosis of low grade non-Hodgkin's lymphoma.

AIM: To analyze the bone marrow (BM) infiltration in low-grade non-Hodgkin's lymphomas (LGNHL) and assess its association with the histopathology type, clinical behavior, and disease prognosis. METHOD: BM smears obtained by needle biopsy and stained by standard methods were analyzed in 60 patients with LGNHL using the Working Formulation. RESULTS: BM infiltration was observed in 57% of the lymphocytic lymphomas (A), in 48% of lymphoplasmocytic/ plasmocytoid lymphomas (AI), and in 31% of follicular lymphomas (follicular small cleaved cell and follicular mixed B and C). The difference was not significant. The 5-year survival rates for patients with and without bone marrow infiltration were 53% and 56% respectively, and 10-year survival rates were 31% and 45% (p>0.05). CONCLUSION: The presence of bone marrow infiltration at diagnosis did not significantly affect the prognosis of LGNHL.

Prognostic relevance of non-Hodgkin's lymphomas cell cycle data.

Determination of proliferative activity of non-Hodgkin's lymphomas (NHL), aimed at improving the prediction of their clinical behavior, has gained considerable attention in the recent years. Flow cytometry has allowed rapid measurement of the cellular DNA content in terms of ploidy and proliferative activity. Flow cytometric DNA analysis was performed on paraffin embedded biopsy specimens taken from 125 patients with NHL. In 90 of them, proliferative index (PI) could be accurately measured and correlated with histology grade of the Working Formulation (WF). Intermediate and high grade NHL (54 patients) were analyzed together as HG-NHL. With the discrimination point for PI of 10%, the survival of high and low proliferative lymphomas was compared in the whole NHL group and within the WF prognostic groups. The median PI was 5% in LG (low grade) NHL and 10% in HG (high grade) NHL group. Acturial survival in NHL with high proliferative activity (39 patients) was 31% at 5 years and 15% at 10 years, and in NHL with low proliferative activity (51 patients) 53% and 18%, respectively (p = 0.002). In HG-NHL, survival at 5 years for low proliferative cases was 55% and for high proliferative cases 28% (p = 0.065), whereas in the LG-NHL group it was 54% and 28%, respectively (p = 0.059). The survival at 10 years was nearly equal in all groups. Proliferative index was associated with the overall survival of NHL in the whole group, as well as within the LG and HG prognostic categories. PI could differentiate more and less aggressive NHLs both within LG-NHL and HG-NHL. A tendency of survival curves toward continuous relapse was observed in low proliferative NHL and a tendency toward "plateau" in high proliferative NHL, irrespective of the histology grade.

Prognosis in monoclonal gammopathy of undetermined significance.

Eighty-seven patients with monoclonal gammopathy of undetermined significance (MGUS) were followed for a period of 1-20 years, median 91 months. Transformation to multiple myeloma occurred in 14 patients of whom seven died as a consequence of the disease. There were 13 unrelated deaths. The actuarial probability of survival was 80% at 10 years and 44% at 15 years and the probabilities of malignant conversion for the same periods were 17% and 30% respectively. The most significant factor influencing the probability of malignant conversion was the increase of monoclonal protein above the level of 30 g/l during the observation period (P<0.001), followed by an increase of M-protein to more than 50% above the baseline level (P=0.02) and a decreased level of uninvolved immunoglobulins (P=0.054).

Prognostic parameters in low-grade non-Hodgkin's lymphomas.

In a group of 73 patients with low-grade non-Hodgkin's lymphomas (LG NHL) a multivariate analysis of the following variables was performed: pathological types following the International Working Formulation, clinical stage, B-symptoms, erythrocyte sedimentation rate, hemoglobin level, white blood cell and lymphocyte count, serum gamma globulin level, serum total lactic dehydrogenase (LDH) level, mitotic and complete remission. The patients with lymphocytic lymphoma manifested the best survival in this group. Low-proliferative lymphomas showed better survival than high-proliferative lymphomas at 3 and 10 years. B-symptoms, serum total LDH level and complete remission were significant independent prognostic factors.