Search PubMed⌕ Search

Biomedical subjects

S Berger

Publications and source records attributed to S Berger.

At least 109 records · Page 6Linked to original sources

Iodoacetate produces striatal excitotoxic lesions.

Impairment of energy production may play a role in the pathogenesis of Huntington's disease (HD). It was recently shown that huntingtin can bind to and possibly inhibit the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found that intrastriatal administration of the GAPDH inhibitor iodoacetate produces striatal lesions that are significantly attenuated by removal of the corticostriatal glutamatergic input, consistent with an excitotoxic mechanism. The lesions are accompanied by increased production of hydroxyl free radicals as assessed by conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid. In vivo magnetic resonance imaging showed lesions on T2-weighted scans, but there was only a small increase in lactate content. These results show that inhibition of GAPDH produces striatal lesions in vivo and suggest that inhibition of GAPDH could contribute to neuronal degeneration in HD.

Animals↗

The effect of dietary alpha-tocopherol on the experimental vasogenic brain edema.

It has become increasingly obvious that free radicals and lipid peroxidation contribute to brain damage from trauma by mediating edema formation and ischemia. It should, therefore, be expected that the actual level of endogenous antioxidants, as for example, vitamin C and E in plasma, has an influence on the extent of free radical-induced injury. In this communication we investigate the effect of dietary changes in the free radical scavenger alpha-tocopherol on posttraumatic cerebral swelling in Sprague-Dawley rats. Low, normal, and high plasma levels of alpha-tocopherol were established by respective diets supplied over 2 weeks. Animals of all groups received the same food without alpha-tocopherol. One group was fed a vitamin E-free diet. The pellet-food for the other animals was supplemented either with 5-mg alpha-tocopherol/100 g or 250-mg alpha-tocopherol/100 g dry mass, respectively. The vitamin E-free diet lowered the alpha-tocopherol level in plasma to 30% of control, whereas supplementation with 250 mg/100 g led to a plasma concentration of 200% of control. The animals were then subjected to a focal cold injury of the left cerebral hemisphere. Twenty-four hours after trauma the brain was removed and the water content of each hemisphere was determined by the wet-dry weight method. Swelling of the traumatized hemisphere was calculated as the difference in weight between the traumatized and contralateral control hemisphere. The 2-week alpha-tocopherol supplementation or -deletion diet, respectively, did not either afford significant reduction or lead to an enhancement of traumatic brain swelling. Likewise, the increase in brain water content of the traumatized hemisphere was not affected. It is concluded that supplementation or depletion of alpha-tocopherol for 2 weeks, resulting in a marked increase or decrease of the vitamin E plasma level, does not influence formation of posttraumatic vasogenic brain edema.

Animals↗

[Outcome of treatment of ingrown toe nails in the child].

Difficulties encountered and long-term results of surgical treatment of ingrown toenails are well documented in the adult patient. In infants and children, however, little is known about this problematic entity. We therefore performed a follow-up study in 91 out of 99 ingrowing toenails in children up to 14 years. The patients were treated in our department from 1990 to 1994 mainly by wedge resection. 64 nail folds remained free of symptoms after single surgical treatment. Recurrence of infection or nail spikes was found in 21 out of 85 nail folds. In children, conservative treatments with antimicrobial ointments, gutter treatment, and in selected cases systemic antibiotics, are more promising than in adults. If these efforts remain unsuccessful, the only reliable surgical approach is a radical wedge resection.

Adolescent↗

Immune complex-induced interleukin-6, interleukin-10 and prostaglandin secretion by human monocytes: a network of pro- and anti-inflammatory cytokines dependent on the antigen:antibody ratio.

We have used two experimental models of immune complexes to study the secretion of interleukin (IL)-10, IL-6 and their connection with the immune complex-induced synthesis of prostaglandin (PG) E2 by human monocytes in vitro. Immune complexes formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum immunoglobulins induced the release of IL-6 and IL-10 in a dose- and antigen: antibody ratio-dependent manner. Antigen-antibody complexes formed near equivalence were most effective in induction of a cytokine response. PGE2 could augment the immune complex-induced IL-6 and IL-10 secretion, but alone, did not induce cytokine secretion. IL-10 was capable of down-regulating the release of IL-6 and PGE2. Additionally, we demonstrated that endogenously synthesized IL-10 limited the immune complex-induced secretion of proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta. All three regulatory factors examined here share anti-inflammatory properties and are closely associated with the T helper type 2 (Th2) immune response. We conclude that immune complexes, besides their well-known ability no cause acute and chronic inflammation, can mediate immunosuppressive effects and influence the balance of Th1/Th2 responses.

Antigen-Antibody Complex↗

Aprotinin improves outcome of single-ventricle palliation.

BACKGROUND: Elevation of pulmonary vascular resistance as a consequence of cardiopulmonary bypass may lead to failure of single-ventricle palliation. We reviewed our experience with aprotinin, a nonspecific serine protease inhibitor, to determine whether it could ameliorate the inflammatory effects of cardiopulmonary bypass and improve outcome of single-ventricle palliation. METHODS: Forty-six consecutive patients undergoing single-ventricle palliation using cardiopulmonary bypass were reviewed retrospectively. Aprotinin was used in 8 of 30 bidirectional cavopulmonary shunt and 10 of 16 Fontan procedures. RESULTS: Aprotinin use was associated with a decrease in the early postoperative transpulmonary gradient among patients undergoing Fontan and bidirectional cavopulmonary shunt procedures. The bidirectional cavopulmonary shunt aprotinin group had a higher oxygen saturation and a decrease in quantity and duration of thoracic drainage. Among patients receiving aprotinin there were no episodes of mediastinitis, thrombus formation, or renal failure. CONCLUSIONS: Aprotinin use in single-ventricle palliation was associated with decreased transpulmonary gradient and increased oxygen saturation consistent with decreased pulmonary vascular resistance. This retrospective study suggests that aprotinin has a favorable impact on the early postoperative course of single-ventricle palliation.

Aprotinin↗

Statistical approach for evolutionary relationship of alpha-conotoxins and members of insulin-superfamily.

Similar conserved structures appear in apparently unrelated protein families. Thus, the superfamily of insulin shows an evolutionary relationship with the alpha-conotoxins of marine fish-hunting snails as indicated by methods of protein comparison. In order to reach statistical significance, the A-chains of different insulins, insulin-like growth factors, relaxins, insulin related peptides from invertebrates were drawn for comparison. These data were correlated with sequences from randomly chosen proteins. The alpha-conotoxins show identity scores up to 37.5% and similarity up to 56.2% toward the members of the insulin-superfamily. These scores conform to values achieved by comparing the relaxin and the insulin/IGF-sequences. The data show clearly that the identity and similarity values obtained in the comparison with the insulins are significantly higher than the scores of randomly chosen protein primary structures. According to our calculated data, this hormone system regulating metabolism and growth in vertebrates and the mentioned toxin-receptor system share the same evolutionary ancestor. However, this statistical approach has to be substantiated on gene level.

Amino Acid Sequence↗

Analysis of glucocorticoid and mineralocorticoid signalling by gene targeting.

To get a better understanding of the role of glucocorticoid and mineralocorticoid signalling during development and in whole animal physiology, we have disrupted the mouse glucocorticoid and mineralocorticoid receptor gene by gene targeting. Most of the mice with a disrupted glucocorticoid receptor gene die within the first hours after birth due to severe lung atelectasis. Perinatal induction of gluconeogenic enzymes in the liver is impaired. Feed back control of the glucocorticoid synthesis via the hypothalamic-pituitary-adrenal axis is perturbed leading to increased plasma levels of corticosterone and adrenocorticotrophic hormone. Increased activity of the hypothalamic-pituitary-adrenal axis results in extensive hypertrophy and hyperplasia of the cortical zones of the adrenal and induction of genes involved in steroid biosynthesis. The adrenal medulla is disorganized and severely reduced in size; cells capable of adrenaline synthesis are missing. Mineralocorticoid receptor deficient mice die around day 10 after birth. Weight loss precedes death of homozygous mutant mice and is correlated with an increase in the haematocrit. As a consequence of this mutation plasma levels of renin, angiotensin II, and aldosterone are highly elevated.

Animals↗

Decreasing period-length of the endogenous circadian rhythm of oxygen evolution in Acetabularia and its possible relation to aging.

Endogenous circadian rhythms observed under constant conditions normally show period length variations. However, a general trend is difficult to identify when cells or organisms are entrained with the usual 24-h-period light/dark cycles. Therefore, these variations in time have been considered as fluctuations. In order to gain more insight into this phenomenon, individual Acetabularia cells were exposed to light/dark cycles of 16 h (LD 8:8) and 33.6 h (LD 16.8:16.8), respectively, i.e., periods which lie distinctly outside the range of the normal circadian entrainment. Employing a high-resolution procedure for data analysis, decreasing period lengths could consistently be detected when cells were kept under constant conditions for several weeks. Possible causes of this decrease are discussed.

Acetabularia↗

Twenty-year experience with repair of complete atrioventricular septal defects.

BACKGROUND: To determine factors predicting mortality and morbidity after repair of complete atrioventricular septal defect, we retrospectively analyzed preoperative, operative, and postrepair factors on the outcome of 115 consecutive complete atrioventricular septal defect repairs at The Children's Hospital of Wisconsin between January 1974 and December 1993. METHODS: For the entire experience the operative mortality was 13.9% (16 patients). During the most recent era, January 1988 to December 1993, operative mortality was 3.6% (2 of 55 patients). This was significantly improved from the two previous eras, January 1974 to December 1980, 28% (7 of 25) and January 1981 to December 1987, 20% (7 of 35 patients) (p = 0.02). There were seven late deaths; 10-year actuarial survival, including operative mortality was 81%. Age at complete repair decreased; before 1982 all patients were more than 12 months of age, whereas after 1982 64% (56 of 88 patients) were 12 months of age or less. RESULTS: Moderate or severe preoperative left atrioventricular valve regurgitation was not a risk factor for operative mortality. For operative survivors with moderate to severe preoperative left atrioventricular valve regurgitation (n = 17), late postoperative left atrioventricular valve regurgitation (follow-up data available on 15 patients) was significantly reduced (severe = 1, moderate = 5, mild = 9; p = 0.007). CONCLUSIONS: Early mortality was predicted by the era of surgical repair. Conversion to routine repair during infancy was achieved with a simultaneous decrease in operative mortality. For patients with moderate to severe preoperative left atrioventricular valve regurgitation, significant improvement in the degree of left atrioventricular valve regurgitation can be expected without an increase in operative or late mortality or morbidity.

Actuarial Analysis↗

O-glycosylation of fibrinogen from different mammalian species as revealed by the binding of Escherichia coli biotinylated lectins.

After the demonstration that neither N-glycans nor neuraminic acid are involved in the binding of K88 lectins to the B beta and gamma chains of porcine fibrinogen and that their recognition was due to O-glycans (L'Hôte C, Berger S, Bourgerie S, Duval-Ifiah Y, Julien R, Karamanos Y. Infect Immun 1995; 63: 1927-1932) it clearly appeared that these lectins could be used as probes to detect O-glycans on fibrinogens of other species. The conclusion of the present study is that many mammalian fibrinogens contain complex O-glycans on B beta and gamma chains. In addition, the combined use of the biotinylated K99 lectin and the Peanut agglutinin demonstrated the presence of sialylated T-antigens on the A alpha chains of all the fibrinogens examined. These lectins can now be used to determine differences on the glycosylation status of fibrinogens within one species and also to detect O-glycans on other glycoproteins.

Animals↗

[Nutrition and mortality from some diet-related diseases].

Authors analysed changes in consumption of selected food groups (cereals, fruit, vegetables, meat, fat, sweets) as well as mortality indexes (CVD, intestinal cancers, diabetes) among four European countries (the Netherlands, United Kingdom, Norway, Sweden) during 1970-1992. It was shown that consumption of fruit and vegetables (except the Netherlands) significantly increased. The growing tendency of meat consumption was decelerated, whereas no changes were observed in case of cereals, total fats and sweets. However (except Sweden) fats of animal origin decreased in favour of vegetable ones. As far as mortality from CVD and stomach cancer is concerned some decrease was observed in all countries. In addition mortality from intestine and colon cancer was lower in Sweden as well as UK. Although changes in dietary pattern are playing the crucial role observed mortality rates, other factors related to style of life incl. smoking or physical activity should not be overlooked.

Adult↗

[Immune complexes induce the secretion of Th2 cytokines in human monocytes].

Two experimental models of immune complexes were used to study the secretion of interleukin (IL)-10, IL-6, IL-1 beta and TNF-alpha by human monocytes in vitro. Immune complexes formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum immunoglobulins induced the release of IL-6 and IL-10 in a dose- and antigen: antibody ratio-dependent manner. Antigen-antibody complexes formed near equivalence were most effective in induction of a cytokine response. Additionally, we demonstrated that endogenously synthesized IL-10 limited the immune complex-induced secretion of proinflammatory cytokines tumor necrosis factor-alpha, IL-6 and IL-1 beta. IL-10 is an anti-inflammatory cytokine and closely associated with the T helper type 2 (Th2) immune response. We conclude that immune complexes, besides their well known ability to cause acute and chronic inflammation, can mediate immunosuppressive effects and influence the balance of Th1/ Th2 responses.

Antigen-Antibody Complex↗

Does an additional source of pulmonary blood flow alter outcome after a bidirectional cavopulmonary shunt?

BACKGROUND: The bidirectional cavopulmonary shunt has become an important intermediate step in the treatment of pediatric patients with single ventricle physiology who are ultimately destined for palliative surgery. We wanted to know whether there would be risks or benefits if an additional source of pulmonary blood flow was left after a bidirectional cavopulmonary shunt. METHODS AND RESULTS: We retrospectively reviewed the medical and surgical records of all patients who underwent a bidirectional cavopulmonary shunt at the Children's Hospital of Wisconsin between January 1991 and December 1993. A total of 43 patients were identified. Anatomic diagnoses included double inlet left ventricle (14 patients), tricuspid atresia (8 patients), pulmonary atresia with intact septum (6 patients), single right ventricle (5 patients), hypoplastic left heart (3 patients), unbalanced atrioventricular septal defect (3 patients), and other complex lesions (4 patients). We then divided the patients into two groups for purposes of analysis. Group 1 had only the cavopulmonary shunt as a source of pulmonary flow (22 patients); group 2 had an additional source of pulmonary flow (21 patients). Patient age at the time of cavopulmonary shunt ranged from 6 months to 12 years, with group 1 patients being younger (31 versus 45 months, P = .05). Group 2 patients had higher postoperative central venous pressures (17.8 versus 14.1 mm Hg, P < .001) and oxygen saturations (86% versus 81%, P < .001) than did group 1 patients. There was no statistical difference between groups in the number of chest tube days or hospital days. There was 1 early death in group 1 related to severe ventricular dysfunction and 1 late death in group 2 related to sepsis. Five patients in group 2 were readmitted to the hospital for drainage of a large chylothorax compared with none in group 1 (P < .02). CONCLUSIONS: We conclude that patients with an additional source of pulmonary blood flow after bidirectional cavopulmonary shunt have higher postoperative central venous pressures, have higher oxygen saturations, and are at risk for the late development of a chylothorax.

Child↗

S15261 antagonises amylin-induced impaired glucose tolerance.

Amylin has been postulated to antagonise or inhibit the action of insulin in peripheral rat tissues and thus contribute to, or be responsible for, the development of insulin resistance. We have recently reported that S15261 is a compound capable of increasing insulin sensitivity in ageing insulin resistant rats. In order to assess whether S15261 had any effects on amylin induced insulin resistance we used a model where amylin causes an impairement in glucose tolerance in an acute manner, by means of an intraportal infusion of the hormone in normal rats. We report here that S15261 can antagonise this amylin-induced impaired glucose tolerance.

Amyloid↗