The potential detection of low-level aerosol isotopes from new civilian nuclear processes.

As the world faces a challenging future in maintaining the commercial availability of radioactive isotopes for medical use, new methods of medical isotope production are being pursued. Many of these are small in size and could effectively operate continuously. With the potential for much shorter retention times, a new suite of isotopes may soon be found in the environment. The authors estimate that many more aerosols containing low-level isotopes of gas/volatile origin could be detectable at short range and times, and a few at longer ranges and times as compared to those released in more common nuclear reactor operations.

Spontaneously arising concurrent ileocaecal adenocarcinoma and renal pelvis transitional cell carcinoma in a rhesus macaque (Macaca mulatta).

A 25-year-old, female rhesus macaque (Macaca mulatta) presented with a history of weight loss despite a normal appetite and supportive care. The animal was humanely destroyed due to poor prognosis. Post-mortem examination revealed a focally extensive, firm, white annular constriction at the ileocaecal junction and an incidental finding of a pale white nodule approximately 0.8 cm in diameter in the left renal pelvis. Based on the microscopical findings, ileocaecal adenocarcinoma and renal pelvis transitional cell carcinoma (TCC) were diagnosed. The use of cytokeratin (CK)-7 and -20 and uroplakin III as potential renal TCC markers was evaluated. The neoplastic cells were labelled intensely with antibodies to uroplakin III, but not to CK-7 or -20. Spontaneous intestinal adenocarcinoma has been documented in the rhesus macaque, but concurrent renal pelvis TCC is highly unusual.

Zap-70-independent Ca(2+) mobilization and Erk activation in Jurkat T cells in response to T-cell antigen receptor ligation.

The tyrosine kinase ZAP-70 has been implicated as a critical intermediary between T-cell antigen receptor (TCR) stimulation and Erk activation on the basis of the ability of dominant negative ZAP-70 to inhibit TCR-stimulated Erk activation, and the reported inability of anti-CD3 antibodies to activate Erk in ZAP-70-negative Jurkat cells. However, Erk is activated in T cells receiving a partial agonist signal, despite failing to activate ZAP-70. This discrepancy led us to reanalyze the ZAP-70-negative Jurkat T-cell line P116 for its ability to support Erk activation in response to TCR/CD3 stimulation. Erk was activated by CD3 cross-linking in P116 cells. However, this response required a higher concentration of anti-CD3 antibody and was delayed and transient compared to that in Jurkat T cells. Activation of Raf-1 and MEK-1 was coincident with Erk activation. Remarkably, the time course of Ras activation was comparable in the two cell lines, despite proceeding in the absence of LAT tyrosine phosphorylation in the P116 cells. CD3 stimulation of P116 cells also induced tyrosine phosphorylation of phospholipase C-gamma1 (PLCgamma1) and increased the intracellular Ca(2+) concentration. Protein kinase C (PKC) inhibitors blocked CD3-stimulated Erk activation in P116 cells, while parental Jurkat cells were refractory to PKC inhibition. The physiologic relevance of these signaling events is further supported by the finding of PLCgamma1 tyrosine phosphorylation, Erk activation, and CD69 upregulation in P116 cells on stimulation with superantigen and antigen-presenting cells. These results demonstrate the existence of two pathways leading to TCR-stimulated Erk activation in Jurkat T cells: a ZAP-70-independent pathway requiring PKC and a ZAP-70-dependent pathway that is PKC independent.

Presynaptic role of cGMP-dependent protein kinase during long-lasting potentiation.

Previous research has suggested that cGMP-dependent protein kinases (cGKs) may play a role in long-term potentiation in hippocampus, but their site of action has been unknown. We examined this question at synapses between pairs of hippocampal neurons in dissociated cell culture. Injection of a specific peptide inhibitor of cGK into the presynaptic but not the postsynaptic neuron blocked long-lasting potentiation induced by tetanic stimulation of the presynaptic neuron. As controls, injection of a scrambled peptide or a peptide inhibitor of cAMP-dependent protein kinase into either neuron did not block potentiation. Conversely, injection of the alpha isozyme of cGK type I into the presynaptic but not the postsynaptic neuron produced activity-dependent potentiation that did not require NMDA receptor activation. Evidence from Western blots, reverse transcription-PCR, activity assays, and immunocytochemistry indicates that endogenous cGK type I is present in the neurons, including presynaptic terminals. These results support the idea that cGK plays an important presynaptic role during the induction of long-lasting potentiation in hippocampal neurons.

Neuroleptic-related dyskinesias in children and adolescents.

BACKGROUND: Few studies have investigated the comparative risk of neuroleptic-related dyskinesias in children and adolescents receiving typical versus newer, atypical antipsychotics. This prospective study was completed to test whether clinical use of atypical antipsychotics is associated with less risk for developing neuroleptic-related dyskinesias than clinical use of typical neuroleptics in an unselected heterogeneous population of seriously emotionally disturbed youths admitted to acute residential treatment. We also tested a novel model of predictive risk for neuroleptic-related dyskinesias in children and adolescents. METHOD: 102 children and adolescents receiving typical neuroleptics, atypical antipsychotics, or the combination were studied. Youths developing neuroleptic-related dyskinesias were compared with youths free of dyskinesias over a 3-month study period on demographic, diagnostic, and treatment variables. Logistic regression was utilized to develop a novel model of predictive risk. RESULTS: Of neuroleptic-treated youths, 5.9% had probable tardive dyskinesia, a rate less than the prevalence of tardive dyskinesia in chronic neuroleptic-treated adults. Use of typical neuroleptics was significantly (p = .03) associated with dyskinesia compared with use of atypical antipsychotics. Four variables including IQ, initial Abnormal Involuntary Movement Scale score, type of antipsychotic, and cumulative number of risk factors accounted for 35.8% of the variance when predicting dyskinetic status. CONCLUSION: Use of atypical antipsychotics appears to be associated with less dyskinesia risk than typical neuroleptics in an unselected group of seriously emotionally disturbed children and adolescents. Results support a cumulative risk model of neuroleptic-related dyskinesia in youths.

Precision substrate targeting of protein kinases. The cGMP- and cAMP-dependent protein kinases.

The cAMP-dependent (PKA) and cGMP-dependent protein kinases (PKG) share a strong primary sequence homology within their respective active site regions. Not surprisingly, these enzymes also exhibit overlapping substrate specificities, a feature that often interferes with efforts to elucidate their distinct biological roles. In this report, we demonstrate that PKA and PKG exhibit dramatically different behavior with respect to the phosphorylation of alpha-substituted alcohols. Although PKA will phosphorylate only residues that contain an alpha-center configuration analogous to that found in L-serine, PKG utilizes residues that correspond to both L- and D-serine as substrates. The PKG/PKA selectivity of these substrates is the highest ever reported.

Variations in astronaut radiation exposure due to anisotropic shield distribution.

The dose incurred in an environment generated by extraterrestrial space radiations within an anisotropic shield distribution depends on the orientation of the astronaut's body relative to the shield geometry. The fluctuations in exposure of specific organ sites due to astronaut re-orientation are found to be a factor of 2 or more in a typical space habitation module and typical space radiations. An approximation function is found that overestimates astronaut exposure in most cases studied and is recommended as a shield design guide for future deep space missions.

Galactic cosmic ray radiation levels in spacecraft on interplanetary missions.

Using the Langley Research Center galactic cosmic ray (GCR) transport computer code (HZETRN) and the computerized anatomical man (CAM) model, crew radiation levels inside manned spacecraft on interplanetary missions are estimated. These radiation-level estimates include particle fluxes, LET (linear energy transfer) spectra, absorbed dose, and dose equivalent within various organs of interest in GCR protection studies. Changes in these radiation levels resulting from the use of various different types of shield materials are presented.

Results using the biofragmentable anastomotic ring for colon anastomosis.

The Biofragmentable Anastomotic Ring (BAR) (Valtrac, Davis & Geck, Inc.) is a newly approved device intended for colonic anastomosis. We have used the device in 47 patients to date. These patients were studied to determine the effectiveness, uses and limitations of this new device. The BAR is similar in concept to the older Murphy "Button" used circa World War I, but it's constructed of polyglycolic acid rather than metal. Anastomosis is effected by placing the two bowel lumens over the device, tying the purse-string sutures snugly, and "clicking" the device closed. The BAR fragments and is passed 2 to 3 weeks postoperatively. The patients ranged from 14 to 82 years of age. Thirty-nine patients were operated on for cancer, four for diverticulitis, and four for colostomy closure. One transverse colectomy (THC), 15 left hemicolectomies (LHC), 23 sigmoid colectomies (SC), two low anterior resections (LAR), four colostomy closures, and two right hemicolectomies were performed. There were no anastomotic leaks and no complications. We found that because of the need to have access distally to "click" the device closed, BAR anastomosis after LAR is rarely feasible. Because of the small lumenal size of the distal ileum, the BAR is seldom usable for ileocolonic anastomosis after right hemicolectomy (RHC). The newly approved 25-mm BAR may change this. We found that the time required to perform an anastomosis with the BAR is equivalent to stapled techniques. At our hospital, the cost of the device is equivalent to one intestinal stapler. Since multiple staplers are used in most colon anastomotic techniques, there is a modest cost advantage for the BAR.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene disruption of the pcbAB gene encoding ACV synthetase in Cephalosporium acremonium.

Plasmid pPS96 was used to disrupt the genomic region immediately upstream of pcbC in C. acremonium by homologous integration. Approximately 4% of the C. acremonium transformants obtained with pPS96 were unable to produce beta-lactam antibiotics. All transformants obtained with other plasmids and isolates which had not been exposed to transforming DNA retained the ability to produce beta-lactams. Enzyme analysis showed that ACV synthetase activity was missing in the beta-lactam-minus pPS96 transformants. Southern copies of pPS96 in all beta-lactam-minus transformants analyzed. However, predictable alterations of the targeted region were not detected. Transformation of antibiotic-minus transformants with plasmid pZAZ4, carrying a wild-type copy of the region targeted for disruption, resulted in restoration of the ability to produce beta-lactams in greater than 80% of the transformants recovered. Location of the pcbAB gene upstream from pcbC was confirmed by comparing the amino acid sequence of internal peptides from purified ACV synthetase with that deduced from the DNA sequence of the region targeted for disruption. The direction of transcription of the pcbAB gene is opposite that of the pcbC gene. Further analysis of amino acid sequence data from ACV synthetase revealed regions of strong similarity with the peptide synthetases responsible for production of tyrocidine and gramicidin S in Bacillus brevis.

Confirmation of clorsulon residues in cattle kidney by capillary gas chromatography-negative-ion chemical-ionization mass spectrometry.

A confirmatory assay for residues of the anthelmintic agent clorsulon [4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide] in cattle kidney tissue has been developed. The assay involves isolation of a drug-containing fraction by solvent extraction, methylation of the analyte, and fused-silica capillary column gas chromatography-negative-ion chemical-ionization mass spectrometry of the pentamethyl derivative of clorsulon. The intensities of four negative ions [m/z 406 and 408 (trichloro species) and m/z 413 and 415 (dichloro species)] are monitored. Confirmation of the presence of drug in an analyte requires that all four ions appear at the appropriate retention time with their intensity ratios within 10-15% of those arising from analysis of the reference standard, methylated clorsulon; the lower limit of detection is 3 ppb. Quantification of the drug is based on the intensity of the m/z 406 ion. Identification and quantification of residues by the gas chromatographic-mass spectrometric assay gave results in good agreement with those obtained with an electron-capture gas chromatographic assay.

Nursing home care.

The intent of this review is to highlight several difficult questions from a personal perspective while caring for debilitated elderly patients in a nursing home. These problems appear to be encountered less frequently in the acute-care setting. Where possible, supporting literature is cited and legal precedent is indicated. The following topics, among others, are discussed: a framework for physicians' ethical decisions, basic ethical principles, typical problems encountered by the physician, and considerations for withholding treatment.

Isolation of two genes that affect mitotic chromosome transmission in S. cerevisiae.

Two DNA sequences that reduce mitotic fidelity of chromosome transmission have been identified: MIF1 and MIF2. MIF1 is a unique sequence located on the right arm of chromosome XII that stimulates loss and recombination for both chromosomes V and VII when present in a high copy number plasmid. MIF1 is not essential for cell division but is necessary for the normal fidelity of chromosome transmission. MIF2 is a unique sequence located 15 cM distal to HIS6 on chromosome IX that induces a high frequency of chromosome VII loss and a lower frequency of chromosome V loss when present in high copy number; it has no effect on mitotic recombination. Disruption of the genomic MIF2 locus was lethal and cells lacking this function arrested division with a terminal phenotype characteristic of a block in DNA replication or nuclear division.

Aerobic exercise training and improved neuropsychological function of older individuals.

The effects of a four month aerobic exercise conditioning program on neuropsychological test performance, depression indices, sensory thresholds, and visual acuity of 55-70 year old sedentary individuals were evaluated. Aerobically trained subjects were compared with two age-matched control groups of subjects: those who trained with strength and flexibility exercises and others who were not engaged in a supervised exercise program. The aerobically trained subjects demonstrated significantly greater improvement on the neuropsychological test battery than did either control group. Depression scores, sensory thresholds, and visual acuity were not changed by aerobic exercise. The pattern of results suggests that the effect of aerobic exercise training was on central rather than on peripheral function. We speculate that aerobic exercise promoted increased cerebral metabolic activity with a resultant improvement in neuropsychological test scores.

Genetic effects of methyl benzimidazole-2-yl-carbamate on Saccharomyces cerevisiae.

The genetic effects of the mitotic inhibitor methyl benzimidazole-2-yl-carbamate (MBC) have been studied in Saccharomyces cerevisiae. MBC had little or no effect on the frequency of mutation. In some experiments MBC caused an increase in the frequency of mitotic recombination; however, this effect was small and not reproducible. The primary genetic effect of MBC was to induce mitotic chromosome loss at a high frequency. Chromosome loss occurred at equal frequencies for all chromosomes tested (13 of 16). Cells which had lost multiple chromosomes were found more frequently than predicted if individual chromosome loss events were independent. The probability of loss for a particular chromosome increased with length of time cells were incubated with MBC. MBC treatment also increased the frequency at which polyploid cells were found. These results suggested that MBC acted to disrupt the structure or function of the mitotic spindle and cause chromosome nondisjunction.

Mitotic chromosome loss induced by methyl benzimidazole-2-yl-carbamate as a rapid mapping method in Saccharomyces cerevisiae.

Mitotic chromosome loss induced by methyl benzimidazole-2-yl-carbamate has been utilized as a rapid and simple method for assigning genes to individual chromosomes in Saccharomyces cerevisiae. This technique relied on the segregation of heterozygous markers in a diploid strain after methyl benzimidazole-2-yl-carbamate treatment due to loss of whole chromosomes. Correlations between the expression of an unmapped gene and that of a previously mapped recessive marker indicated chromosomal linkage. Depending on whether the unmapped gene and the marker were located in coupling or in repulsion, either positive or negative correlations were seen. The chromosomal location of several previously mapped genes were confirmed as a test of the method, and one previously unmapped gene, nib1, was mapped.

A dependent pathway of gene functions leading to chromosome segregation in Saccharomyces cerevisiae.

Methyl-benzimidazole-2-ylcarbamate (MBC) inhibits the mitotic cell cycle of Saccharomyces cerevisiae at a stage subsequent to DNA synthesis and before the completion of nuclear division (Quinlan, R. A., C. I. Pogson, and K, Gull, 1980, J Cell Sci., 46: 341-352). The step in the cell cycle that is sensitive to MBC inhibition was ordered to reciprocal shift experiments with respect to the step catalyzed by cdc gene products. Execution of the CDC7 step is required for the initiation of DNA synthesis and for completion of the MBC-sensitive step. Results obtained with mutants (cdc2, 6, 8, 9, and 21) defective in DNA replication and with an inhibitor of DNA replication (hydroxyurea) suggest that some DNA replication required for execution of the MBC-sensitive step but that the completion of replication is not. Of particular interest were mutants (cdc5, 13, 14, 15, 16, 17, and 23) that arrest cell division after DNA replication but before nuclear division since previous experiments had not been able to resolve the pathway of events in this part of the cell cycle. Execution of the CDC17 step was found to be a prerequisite for execution of the MBC-sensitive step; the CDC13, 16 and 23 steps are executed independently of the MBC-sensitive step; execution of the MBC-sensitive step is prerequisite for execution of the MBC-sensitive step; execution of the MBC-sensitive step is prerequisite for execution of the CDC14 and 23 steps. These results considerably extend the dependent pathway of events that constitute the cell cycle of S. cerevisiae.