Adaptive functioning following traumatic brain injury and orthopedic injury: a controlled study

BACKGROUND: In an effort to intensify osteosarcoma therapy, systemic ifosfamide was added pre- and postoperatively to an already aggressive three-drug regimen. In a subgroup of patients, loco-regional treatment intensification was attempted by using the intraarterial route to give cisplatin. PATIENTS AND METHODS: Patients < or = 40 years at diagnosis of a localised, de novo high-grade central extremity osteosarcoma were eligible for inclusion into study COSS-86 if registered within three weeks from biopsy. Doxorubicin, high-dose methotrexate, and cisplatin were given to all patients. Patients who fulfilled one or more of three defined high-risk criteria received early systemic treatment intensification by adding ifosfamide as the fourth agent. Preoperatively, these high-risk patients received cisplatin either intraarterially or intravenously. RESULTS: 171 eligible patients were entered, of which 128 were stratified into the high-risk group. When all 171 were analysed by intention-to-treat, actuarial overall and event-free survival rates at ten years were 72% and 66%, respectively. No benefit of intraarterial cisplatin application was detected. Cumulative treatment toxicity was considerable. CONCLUSIONS: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.     

Differential chromosome sensitivity to 5-azacytidine in Alzheimer''s disease

The chemiluminescence (CL) technique with scavengers for superoxide anion (superoxide dismutase) and hydrogen peroxide (catalase) was used to characterize the generation of reactive oxygen species (ROS) inside and outside the human neutrophil after stimulation with both soluble (formyl-methionyl-leucyl-phenylalanine, FMLP) and particulate (urate crystals, zymosan, oxidized LDL) stimuli. Depending on the stimulus used, ROS generation differed in composition and absolute amounts. The ratio between extracellularly and intracellularly produced ROS ranged from 0.3 (zymosan) to 4.2 (FMLP). While enhancing substantially FMLP-stimulated CL, horseradish peroxidase inhibited CL induced by particulate stimuli by 40-80%. Furthermore, an azide-insensitive and therefore peroxidase-independent part of CL was found in FMLP-, LDL- and zymosan-stimulated cells. The results indicate that different agonists may lead through distinct chemical pathways to neutrophil luminol-amplified light generation.     

Effect of mild acid treatment on the survival, enteropathogenicity, and protein production in vibrio parahaemolyticus

Vibrio parahaemolyticus is an important food-borne enteropathogen that encounters various adverse conditions in its native environment or during infection. Effects of mild acid treatment on survival under stress conditions, enteropathogenicity, and protein production in this pathogen were investigated. Logarithmically grown cells, at pH 7.5 shifted to pH 5.0 for 30 min, were more resistant to subsequent acid challenge at pH 4.4. A two-phase adaptive procedure (pH 5.8 for 30 min; pH 5.0 for 30 min) was better than a single-phase procedure for enhancing the acid tolerance of this pathogen. The acid-adapted cells were cross-protected against the challenges of low salinity and thermal inactivation. One-dimensional polyacrylamide gel electrophoresis revealed that proteins with molecular masses of 6.4, 9.0, 13.6, 16.3, 18.9, 22.9, 24.4, 28.3, 33. 9, 36.9, 41.2, 47.6, 58.1, 65.6, 80.5, 88.2, and 96.9 kDa were induced or significantly enhanced, while proteins of 25.3, 30.1, 30. 7, and 91.7 kDa were significantly inhibited. Two-dimensional polyacrylamide gel electrophoresis revealed that 20 species of proteins were induced or significantly enhanced, while 26 species were inhibited. In assays conducted using the suckling mouse model, enteropathogenicity of the acid-adapted cells was significantly enhanced in terms of intestine/body weight ratio and in vivo recovery of infected cells.     

Pneumococcal polysaccharide vaccine in children with chronic renal disease: a prospective study of antibody response and duration

We studied the antibody response to pneumococcal serotypes 3 and 14 after pneumococcal polysaccharide vaccine was administered to 41 children with renal disease. One month after vaccination, 76% and 61% of patients achieved at least a twofold titer rise to serotypes 3 and 14, respectively; this finding was comparable to historic control values. One year after vaccination, the majority of patients retained protective antibody levels. Achieving a titer > or = 1.0 microgram/ml IgG at 1 month was highly predictive of retaining a protective antibody level > or = 0.15 microgram/ml at 1 year.     

Prediction of postoperative knee flexion in Insall-Burstein II total knee arthroplasty

Postoperative knee flexion in patients undergoing Insall-Burstein-II total knee arthroplasty at 2 years was evaluated regarding two basic questions: what groups of patients gain or lose the most flexion and what groups of patients have the best or worst postoperative flexion. Thirteen preoperative variables (maximum flexion, flexion arc, tibiofemoral angle, quadriceps strength, extensor lag, Knee Society score, Knee Society patient assessment, gender, age, height, weight, diagnosis, and surgeon) and four postoperative variable (leg length change, tibiofemoral angle, distance from patella to the joint line, and the tibial prosthesis anteroposterior translation on a lateral radiograph) were used in an attempt to explain postoperative flexion. The analysis was performed on 164 consecutive Insall-Burstein-II total knees in which the data were gathered prospectively on a time oriented medical record database. A regression tree analysis was used to identify several groups of patients, characterized by preoperative factor values, who had markedly above average performance on postoperative flexion. The preoperative factors identified include preoperative flexion, flexion arc, tibiofemoral angle, extensor lag, diagnosis, and age. The only postoperative variable of significance was tibiofemoral angle. Among the potential determinants of postoperative flexion that failed to appear predictive were the Knee Society scores and surgeon. Preoperative flexion is known to be a critical determinant of postoperative flexion in total knee replacement. However, in the current study, preoperative flexion accounted for only half of the difference between the best (122 degrees) and the worst (88 degrees) group, as determined with regression tree analysis.     

Conformal proton therapy for prostate carcinoma

The suppression of apoptosis may contribute to the carcinogenicity of the peroxisome proliferators (PPs), a class of non-genotoxic rodent hepatocarcinogens. Our previous work demonstrated that the PP nafenopin suppressed both spontaneous and transforming growth factor beta1 (TGFbeta1)-induced hepatocyte apoptosis both in vivo and in vitro. Here, we extend these observations by demonstrating the ability of nafenopin to suppress apoptosis induced by other major candidates for the signalling of cell death in the liver. Treatment of rat or mouse hepatocyte monolayers with TGFbeta1 or the DNA damaging drugs etoposide or hydroxyurea induced high levels of apoptosis. Western blot analysis did not support a role for either p53 or p21waf1 in etoposide-induced apoptosis in rat hepatocytes. Treatment of mouse hepatocytes with an agonistic anti-Fas antibody also resulted in an induction of high levels of apoptosis. Pre-addition and continued exposure to nafenopin suppressed apoptosis induced by all three stimuli. Overall, our studies demonstrate that the ability of nafenopin to protect hepatocytes from apoptosis is not restricted to species or apoptotic stimulus. It is possible, therefore, that the PPs may suppress apoptosis by acting on diverse signalling pathways. However, it seems more likely that nafenopin suppresses hepatocyte apoptosis elicited by each death stimulus by impinging on a core apoptotic mechanism.     

Oceanic protection of prebiotic organic compounds from UV radiation

It is frequently stated that UV light would cause massive destruction of prebiotic organic compounds because of the absence of an ozone layer. The elevated UV flux of the early sun compounds this problem. This applies to organic compounds of both terrestrial and extraterrestrial origin. Attempts to deal with this problem generally involve atmospheric absorbers. We show here that prebiotic organic polymers as well as several inorganic compounds are sufficient to protect oceanic organic molecules from UV degradation. This aqueous protection is in addition to any atmospheric UV absorbers and should be a ubiquitous planetary phenomenon serving to increase the size of planetary habitable zones.     

The Interactive Effects of Task and External Feedback on Practice Performance and Learning

Just a few decades ago, the saccharides bound to glycoproteins were considered little more than an irritation. They increased the difficulty of purifying and characterizing proteins, making proteins run as several bands on gels and smearing them on columns. They were considered a nuisance and were typically cleaved away to reveal the 'important part', the protein moiety, for structural (e.g. via X-ray crystallography or nuclear magnetic resonance) and functional studies. We now realize that that the saccharide is often as important as the protein itself, and that glycosylation can have many effects on the function, structure, physical properties and targeting of a protein. There are a myriad of reviews and books on this subject, reflecting the nearly overwhelming number of articles in print discussing saccharide structures, glycoprotein processing enzymes and the biological implication of glycosylation. This review discusses, in turn, the extent and biological relevance of glycosylation; the structures observed; how glycosylated proteins are formed in vivo; the clinical relevance of glycosylation, in terms of the correlations between disease states and unusual glycosylation patterns; and, finally, the molecules, both natural and synthetic, that can be used to study the role of carbohydrates in glycoprotein structure and function or to disrupt various carbohydrate recognition processes and enzymatic reactions in the glycoprotein synthetic pathway.