Immunoregulatory markers in rats carrying Dunning R3327 H, G, or MAT-LyLu prostatic adenocarcinoma variants

The Dunning R3327 tumor represents a system for studying prostate cancer in Copenhagen X Fischer rats. Animals bearing variant sublines (H, G, and MAT-LyLu) differing in growth rate, differentiation, hormone responsiveness, and metastatic ability were assayed for three immunological markers. Spleens were passed through a tissue sieve, and mononuclear cells were obtained by Ficoll-Hypaque centrifugation. These were assayed for leukocytic subsets using monoclonal antibodies. An adherent population was isolated and evaluated using thin-layer chromatography for conversion of radiolabeled arachidonic acid to E series prostaglandins. Finally, sera from these animals were assayed for levels of circulating immune complexes using polyethylene glycol precipitation. Data from 52 rats bearing the various tumors were obtained, correlated with subline aggressiveness, and compared to 15 controls. Each tumor group demonstrated significantly lower helper/suppressor T-cell ratios than controls, probably due to general tumor presence. In addition, the most aggressive R3327 MAT-LyLu variant had significantly increased prostaglandin E synthesis by adherent spleen cells compared to the H or G sublines and significantly increased levels of circulating immune complexes relative to the H subline. G subline values for both prostaglandin E and circulating immune complexes levels were intermediate, suggesting that these markers correlate better with tumor aggressiveness than helper/suppressor T-cell ratios.     

Asbestos-related focal lung masses: manifestations on conventional and high-resolution CT scans

In 260 asbestos-exposed individuals evaluated by means of computed tomography (CT), 43 unsuspected pulmonary masses were found in 27 individuals. The masses included fissural pleural plaques (n = 10), dense fibrotic bands (n = 3), round atelectasis (n = 11), carcinomas (n = 3), and other presumed benign masses (n = 16). The most helpful features in the diagnosis of rounded atelectasis with CT were (a) contiguity to areas of diffuse pleural thickening, (b) a lentiform or wedge-shaped outline, (c) evidence of volume loss in the adjacent lung, and (d) a characteristic "comet tail" of vessels and bronchi sweeping into the margins of the mass. Less advanced areas of focal atelectasis had fewer classic features. Intrafissural pleural plaques were readily identified with high-resolution CT. In asbestos-related masses, the demonstration of stability over time is necessary. Careful interpretation of CT and high-resolution CT features and close surveillance can obviate the need for biopsy in the majority of instances.     

Outbreak of Pichia anomala infection in the pediatric service of a tertiary-care center in Northern India

An outbreak of nosocomial fungemia due to the unusual yeast, Pichia anomala occurred in the pediatric wards of our hospital over a period of 23 months (April 1996 to February 1998). A total of 379 neonates and children (4.2% admissions) were infected. The probable index case was admitted to the pediatric emergency ward, with subsequent transmission to the premature nursery, pediatric intensive care units, and other children wards. Carriage on the hands of health care personnel was likely to be responsible for dissemination of the fungus. The outbreak could only be controlled after a health education campaign to improve hand-washing practices was instituted and after nystatin-fluconazole prophylaxis to all premature neonates and high-risk infants was introduced. In a case-control study, we identified a lower gestational age, a very low birth weight (<1,500 g), and a longer duration of hospital stay as significant risk factors associated with P. anomala fungemia in premature neonates. We conducted a culture prevalence survey of 50 consecutive premature neonates and found that 28% were colonized with P. anomala at a skin or mucosal site on the date of delivery and that 20% of these neonates subsequently developed P. anomala fungemia. We performed multilocus enzyme electrophoresis on 40 P. anomala outbreak isolates (including patient and health care workers' hand isolates), and the results suggested that these isolates were identical. Our study highlights the importance of P. anomala as an emerging nosocomial fungal pathogen.     

The missions of medical schools: the pursuit of health in the service of society

Mission statements and role documents of medical schools in the United Kingdom, United States, Canada and Australia have been examined on their Internet Web sites and categorised in purpose, content and presentation. The format and content are highly variable, but there is a common vision of three integral roles, namely, education, advancement of knowledge and service to society. Other frequent themes include tradition and historical perspective, service for designated communities, and benchmarking to accreditation standards. Differences in content reflect variable interpretation of the notion of "mission", and local or national characteristics such as institutional affiliations, the types, levels and organisation of medical education, relationships with health systems, and extent of multi-professional education. Outcomes data and measures of medical school performance referenced to the institution's stated missions are rarely encountered.     

Activated Ras/JNK driven Dilp8 in imaginal discs adversely affects organismal homeostasis during early pupal stage in Drosophila,a new checkpoint for development

Background

Dilp8-mediated inhibition of ecdysone synthesis and pupation in holometabolous insects maintains developmental homeostasis through stringent control of timing and strength of molting signals. We examined reasons for normal pupation but early pupal death observed in certain cases.

Results

Overexpression of activated Ras in developing eye/wing discs inhibited Ptth expression in brain via upregulated JNK signaling mediated Dilp8 secretion from imaginal discs, which inhibited ecdysone synthesis in prothoracic gland after pupariation, leading to death of ~25- to 30-hour-old pupae. Inhibition of elevated Ras signaling completely rescued early pupal death while post-pupation administration of ecdysone to organisms with elevated Ras signaling in eye discs partially rescued their early pupal death. Unlike the earlier known Dilp8 action in delaying pupation, hyperactivated Ras mediated elevation of pJNK signaling in imaginal discs caused Dilp8 secretion after pupariation. Ectopic expression of certain other transgene causing pupal lethality similarly enhanced pJNK and early pupal Dilp8 levels. Suboptimal ecdysone levels after 8 hours of pupation prevented the early pupal metamorphic changes and caused organismal death.

Conclusions

Our results reveal early pupal stage as a novel Dilp8 mediated post-pupariation checkpoint and provide further evidence for interorgan signaling during development, wherein a peripheral tissue influences the CNS driven endocrine function.

     

P300 and Long-Term Memory: Latency Predicts Recognition Performance

The study-test paradigm was used to investigate memory acquisition processes and the effects of repetition on long-term recognition memory. In this procedure, subjects are presented with a list of words (“targets”) to be memorized (Study series). They are later tested for recognition on a word list comprised of the target words mixed randomly with an equal number of new, distractor words (Test series). Both reaction time and the P300 component of the event-related brain potential were used as measures of processing time. During the Study series, large P300s were elicited despite a word category probability of 1.0. When the words from the Study series were divided on the basis of recognition performance, words that were subsequently recognized elicited P300s with shorter latencies than unrecognized words. P300 amplitude to words in the Study series increased with repetition while maintaining a constant latency. During the Test series, P300 latency and reaction time decreased with repetition for both target and distractor words. P300 amplitude to all words increased substantially over Test repetitions with target words eliciting larger P300s than distractor words. Words that were recognized more consistently during the Test series elicited larger and earlier P300s than words that were recognized less consistently. The P300 amplitude and latency results from both the Study and Test series are interpreted as reflecting the increased discriminability of the target words as the memory trace increases in strength.     

Changes in myocardial pyrimidine nucleotide levels following repeated injections of isoproterenol in rats

Changes which might lead to the initiation of cardiac hypertrophy include possible variations in the dynamics of nucleotides. In the experiments reported in this paper, changes in the pool sizes of adenine, uracil and cytosine nucleotides were observed during the initial phase of cardiac overload.Repeated subcutaneous injections of isoproterenol (ISO) (5 mg·kg^–1 body weight, s.c.) were performed so as to produce symmetric cardiomegaly in rats. Under these conditions, the dry weight of the heart, on the fifth day of dialy injections of ISO, had increased by 43% and the RNA concentration by 39%. There was no significant change in the DNA concentration. No further changes in weight or in DNA and RNA concentrations were recorded from the fifth to the tenth day of treatment.Changes in UTP and ATP were carefully monitored during the first days following ISO application. The levels of both nucleotides decreased sharply at first. The ATP level remained below the control value for at least 48 h while the UTP level was rapidly restored and a further increase occurred resulting in a maximal enlargement of 82% after the 12th h. At the same time, the uracil nucleotide pool and the cytosine nucleotide pool had increased by 76% and 101%, respectively, while the adenine nucleotide content of the myocardium remained 15% below control level. Repeated injections of ISO induced effects on ATP and UTP levels which were similar in direction but attenuated.The significance of an increase in the pyrimidine nucleotide pools in relation to nucleic acid synthesis is discussed.     

Development and Evaluation of a Tetraplex Flow Cytometric Assay for Quantitation of Serum Antibodies to Neisseria meningitidis Serogroups A, C, Y, and W-135

A rapid and simple method for the simultaneous quantitation of serum immunoglobulin G (IgG) antibodies specific for Neisseria meningitidis serogroups A, C, Y, and W-135 was developed and evaluated. Four bead sets were generated, each conjugated with one of the meningococcal capsular polysaccharides (A, C, Y, or W-135) and serologically assessed by the use of antimeningococcal international reference sera. Cross-reactivity studies demonstrated no inhibition between monoplex and multiplex assays, and the assay was linear over a 24-fold serum dilution range. Inhibition studies demonstrated that the assay is specific, with <25% heterologous inhibition occurring. The assay was also found to have low intra- and interassay variations and limits of detection ≤650 pg/ml. A comparison of the meningococcal bead assay with the standardized meningococcal enzyme-linked immunosorbent assay showed a good correlation between the IgG concentrations obtained by each assay. The tetraplex assay has the potential to be an important addition to the serologic evaluation of meningococcal capsular polysaccharide conjugate vaccines.