Identification of a unique form of p53 in human cord blood associated with the development of maternal autoantibodies

PROBLEM: The possible link between p53-reactive antibodies in multiparous women and exposure to a unique p53 protein during pregnancy was examined. METHOD OF STUDY: p53-reactive antibodies were evaluated in sera from nulligravid and multiparous women and patients with ovarian cancer by Western immunoblot. Furthermore, the presence of p53 protein was assayed in cord blood by enzyme-linked immunosorbent assay. Cord blood-derived p53 was compared structurally by protein fingerprinting and functionally by gel mobility shift assay to other isolates of p53. RESULTS: Antibodies reactive with wild-type p53 were observed in 92% of multiparous women and 42% were reactive with one tumor-derived p53 protein. p53 protein was detected in 27 of 154 samples of cord blood. Structural analysis indicated that the fetal p53 resembled the UL-1 p53. Functionally, the fetal and UL-1 protein failed to bind DNA. CONCLUSIONS: Fetal p53 protein seems to be distinct from wild-type p53, characterized by enhanced stability, structural differences and inability to bind DNA, analogous to alternatively spliced variants. Exposure to fetal p53 protein may form the basis for immunologic protection against cancer induced by multiparity.     

A transformation method for stochastic control problems with partial observations

Two stochastic control problems with partial observations are studied, one where the policy or control law depends only on the latest observation (the controller does not have recall of observations), and the other with the standard partial observations model. The equivalent full observation problems are formulated, and the equivalence is proven using a new method. The results are illustrated with a simple example.     

Prediction of recurrent choledocholithiasis by quantitative cholescintigraphy in patients after endoscopic sphincterotomy

BACKGROUND: Endoscopic sphincterotomy (EST) is widely used for the removal of stones from the bile duct, but stones recur in about one fifth of patients. AIMS: To investigate hepatic clearance by quantitative cholescintigraphy (QC) in patients after EST and to discern the relationship between biliary emptying and stone recurrence. METHODS: One hundred and forty nine patients who had EST and clearance of the bile duct for choledocholithiasis were selected. All patients were confirmed to have complete EST by sphincter of Oddi manometry and underwent QC soon after normalisation of liver function. Regular clinical follow up was performed for each patient. RESULTS: During a mean 36 month follow up, 22 (14.8%) patients developed recurrent stones in the bile duct. Irrespective of the status of the gall bladder, patients with recurrent stones had a slower hepatic clearance of radioisotope during QC compared with patients without stone recurrence, but only the differences in cholecystectomised patients had statistical significance. After carrying out multivariate analysis, one parameter of QC, percentage clearance of maximal count at 45 minutes, was found to be the only significant factor for stone recurrence. All recurrent stones in the common bile duct were successfully removed at endoscopy. CONCLUSION: Slower hepatic clearance as shown by QC is an important factor responsible for stone recurrence after sphincter ablation.     

CYFRA 21-1 enzyme-linked immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer

BACKGROUND: The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer. METHODS: CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. RESULTS: The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1). CONCLUSION: For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.     

An ultrastructural study of p75 neurotrophin receptor-immunoreactive fiber terminals in the reticular thalamic nucleus of young rats

The reticular thalamic nucleus (RT) receives cholinergic fibers from both the basal forebrain and the brainstem. Recent studies have shown that the p75 neurotrophin receptor (p75NTR) is synthesized in cholinergic neurons in the basal forebrain but not in those in the brainstem. In this study, to identify cholinergic fibers originating from the basal forebrain, we used a monoclonal antibody against p75NTR (192-IgG) and characterized the ultrastructure of the immunoreactive fiber terminals in the rostral part of the RT in 3-week-old rats. Light microscopy revealed that p75NTR-immunoreactive fine fibers and varicosities were distributed throughout the nucleus. From electron micrographs, three types of labeled terminals were identified. The first type of labeled fiber terminals (63 out of 106) was consistently small, contained densely packed vesicles, and established asymmetrical synaptic contacts with heavy and bushy postsynaptic thickening on distal dendritic profiles; the second type (18 out of 106) established asymmetrical synaptic contacts with very slight postsynaptic thickening; and the third type (25 out of 106) of labeled terminals contained pleomorphic vesicles and established symmetrical synaptic contacts with more proximal dendritic surfaces than the first two types. In addition to the above, labeled dendritic profiles receiving non-labeled asymmetrical and symmetrical synaptic contacts were identified. These findings suggest that the basal forebrain cholinergic system establishes a variety of synaptic connections in the RT and influences cortical activity indirectly via thalamocortical pathways, as well as via direct projections to the cortex.     

Amorphous Ni-Mo-P diffusion barrier deposited by non-isothermal deposition

Ni-Mo-P barrier layers deposited on silicon wafers without Pd activation pretreatment were prepared using the non-isothermal deposition (NITD) method in an acidic electroless bath. The operating conditions for fabricating the Ni-Mo-P barrier layers were presented, and the effect of the pH values on the film composition, electric resistivity and thermal stability have been investigated. The thicknesses of Ni-Mo-P films are around 15-20 nm in acidic bath. Our results indicate increasing amounts of Mo and decreasing amounts of P with increasing pH. The electric resistivity decreased with increasing pH value due to the increase of the Mo content in the Ni-Mo-P film. The amorphous structure was formed at pH 3 and 4, but a quasi-amorphous structure was formed at pH 5. Based on our experimental results, the thermal stability of Ni-Mo-P film prepared at pH 4 remains stable up to 650 °C for 1 h annealing.     

A simple proof of the optimality of a threshold policy in a two-server queueing system

Lin and Kumar (1984) introduced a control model with a single queue and two heterogeneous servers. They showed, using policy iteration, that the slower server should only be used if the queue length is above a certain level, i.e., the optimal policy is of threshold type. In this note we give a simple iterative proof of this result.     

Cinedefecography and electromyography in the diagnosis of nonrelaxing puborectalis syndrome

A prospective study was undertaken to assess the correlation between electromyography (EMG) and cinedefecography (CD) for the diagnosis of nonrelaxing puborectalis syndrome (NRPR). Clinical criteria for NRPR included straining, incomplete evacuation, tenesmus, and the need for enemas, suppositories, or digitation. EMG criteria included failure to achieve a significant decrease in electrical activity of the puborectalis (PR) during attempted evacuation. CD criteria included either paradoxical contraction or failure of relaxation of the PR along with incomplete evacuation. In addition, other etiologies for incomplete evacuation, such as rectoanal intussusception or nonemptying rectocele, were excluded by proctoscopy and defecography in all cases. One hundred twelve patients with constipation, 81 females and 31 males, with a mean age of 59 (range, 12-83) years were studied by routine office evaluation, CD, and EMG. Forty-two patients (37 percent) had evidence of NRPR on CD (rectal emptying: none, 24; incomplete, 18). Twenty-eight of these patients (67 percent) also had evidence of NRPR on EMG. EMG findings of NRPR were present in 12 of 70 patients (17 percent) with normal rectal emptying. Conversely, 14 of 72 patients (19 percent) with normal PR relaxation on EMG had an NRPR pattern on CD. The sensitivity and specificity for the EMG diagnosis of NRPR were 67 percent and 83 percent, and the positive and negative predictive values were 70 percent and 80 percent, respectively. Conversely, if EMG is considered as the ideal test for the diagnosis of NRPR, CD had a sensitivity of 70 percent, a specificity of 80 percent, and positive and negative predictive values of 66 percent and 82 percent, respectively. In summary, sensitivity, specificity, and predictive values of EMG and CD are suboptimal. Therefore, a combination of these two tests is suggested for the diagnosis of NRPR.     

A novel model-based approach to optimization and control design of batch processes

Traditionally, many industrial batch processes have been operated according to rigid recipies, in spite of the fact that production would yield more profit or a better product if they were efficiently adapted to changes in quality and cost of the used and/or produced products, process and scheduling conditions, and so on. In this paper a approach, called the flexible recipe approach, is given, which transforms the common rather static recipes into recipes that can be easily improved and used for systematic and efficient production adaptation at the start of a batch and during the processing. To be able to use this approach in an industrial environment a practical implementation is made in the software package FRIS. A fermentation process chosen as an example shows the methods and gives an indication of the expected profit.     

Early calcifications in human coronary arteries as determined with a proton microprobe

The current paradigm reads that calcifications characterize the advanced and complex lesions in the atherosclerotic process. To explore the possibility that coronary artery wall calcifications already commence at an early stage of atherosclerosis, a combination of proton beam techniques with a (sub-) micrometer resolution, i.e., micro-proton induced X-ray emission, backward and forward scattering spectroscopy, was applied on human coronary arteries with lesions preceding overt atheromas. The detection limits of phosphorus and calcium in each separate pixel, 0.88*0.88 microm2 in size, were approximately 150 and 80 microg/g dry weight, respectively. Calcium distributions of entire coronary artery cross section were obtained, and calcifications were demonstrated at a preatheroma stage of the atherosclerotic process. The size of the microcalcifications varied between 1 and 10 microm. The composition of the microcalcifications was deduced from the calcium-to-phosphorus ratio. In order to quantify this ratio, the thickness of the specific X-ray absorber used for PIXE had to be accurately determined. Also, thick target PIXE calculations were performed and the method was validated. The calcium-to-phosphorus ratios of the microcalcifications were assessed with good accuracy and varied from 1.62 to 2.79, which corresponds with amorphous calcium phosphate.