Evaluation of cisplatin treatment given concurrently with pulsed irradiation in cisplatin sensitive and resistant human ovarian carcinoma cell lines.

The aim was to investigate the effect of combined treatment of cisplatin with acute or pulsed radiation in human ovarian carcinoma cells sensitive and resistant to cisplatin. Human ovarian cancer cell parental line A2780s and a derivative cisplatin-resistant line A2780cp were given cisplatin treatment before a single acute dose irradiation or concurrently during a pulsed-dose irradiation sequence. Cells were irradiated in the confluent state, trypsinized and plated after treatment. When the combined treatment for cisplatin was given before acute irradiation, the results showed additive to superadditive effects for both cell lines. However, the superadditivity was only significant in the sensitive cell line. For the concomitant treatment of cisplatin during pulsed-dose irradiation the results were additive, except for the highest cisplatin dose in the A2780cp line where subadditivity was observed. The results indicate that the combined treatments could be clinically useful even though the results are mostly not superadditive. However, high-dose cisplatin (3 microg ml(-1)) caused a subadditive effect in the resistant cell lines for pulsed irradiation. Thus, high-dose cisplatin to overcome resistance is not effective. Cisplatin with both acute and pulsed irradiation showed additive effects indicating no advantage of using cisplatin in pulsed irradiation where sublethal damage repair may be greater.

Cisplatin sensitization by concurrent mild hyperthermia in parental and mutant cell lines deficient in homologous recombination and non-homologous endjoining repair.

The effect of mild hyperthermia on cisplatin sensitization was examined in two cell line pairs, CHO parental AA8 and irsISF, an XRCC3 mutant (deficient in homologous recombination repair), and mouse parental MEF and knockout Ku80 mutants (deficient in non-homologous endjoining repair). The results showed that mild hyperthermia 40, 41 and 42 degrees C given concurrently with cisplatin treatment caused significant sensitization. The degree of sensitization was comparable for the parental and mutant lines, indicating that these repair pathways were likely not involved in cisplatin thermal sensitization. The shorter concurrent treatments cause a larger sensitization than the longer treatments. The reasons for this are not clear, but thermotolerance may be a factor.

Elaboration of microbiological guidelines as an element of codes of hygienic practices for small and/or less developed businesses to verify compliance with hazard analysis critical control point.

Effective assurance of microbiological food safety practices in small and/or less developed businesses is not yet resolved. Although a start has been made by drafting hygiene codes, feasible methods for verifying manufacturing processes that rely on strict and meaningful criteria to be applied to process points are still lacking. This investigation is a model study with various types of ready-to-eat foods aimed at verifying adequate processing for safety and subsequent meticulous hygienic handling and safe storage of foods in small and/or less developed businesses by the use of quantitative methods for selected indicator organisms, as standardized by the International Organization for Standardization. The manufacture of the foods that were used in this study invariably included (i) a heat processing step that ensured a level of lethality of nonsporing organisms at least equivalent to the reduction of such organisms attained in the pasteurization of milk and (ii) effective means of prevention of postprocess recontamination and recolorization. The results of this study indicate that simple microbiological criteria used for this purpose, including aerobic mesophilic colony (standard plate) counts, Enterobacteriaceae counts, and, in some instances, enumeration of yeast propagules, allow adequate verification of good practices throughout. This verification through monitoring of samples taken during processing in small and/or less developed businesses was found to be an attractive alternative to the conventional examination of end products.

A comparison of neuropsychological and situational assessment for predicting employability after closed head injury.

The relationships among neuropsychological assessment, situational assessment, and judgments of future employability in 127 survivors of moderate to severe closed head injury were evaluated. Participants received a comprehensive neuropsychological battery and a situational vocational evaluation. Two groups were created, based on employment recommendation from the situational evaluation. A seven-factor model was found to account for the preponderance of variance within the neuropsychological battery used, and one factor was predictive of group assignment from situational assessment. However, the present data reinforce the predominance of findings in the literature that indicate that, in general, no individual neuropsychological test can be used to predict vocational performance in more environmentally relevant environments. Exceptions to this "rule" may occur when comparisons between results of formal neuropsychological tests and situational evaluation are limited to very simple, very circumscribed, and/or very well-defined functions. Thus, situational assessment is seen as a critical adjunct to neuropsychological assessment in making "real-world" predictions. The particular situational assessment used in this study was internally valid, an important finding given the importance of situational assessment in ecologically valid predictions.

Effects of task size on work-related and aberrant behaviors of youths with autism and mental retardation.

The effects of task size on rate of responding and on-task behavior as well as on nontask-related behaviors of students with autism and mental retardation on a repetitive task under conditions of no reinforcement for responding was analyzed. Task size, defined as the presence of either 36 or 250 beads in a container at the onset of the session, was compared in an alternating treatment design. The small-task condition resulted in higher on-task behavior for all participants and in higher work rate for four of the five participants. For the four participants who engaged in inappropriate use of task materials, higher levels of this behavior occurred in the large-task conditions. Other nontask-related behaviors were higher in the large-task condition for all participants with the exception of stereotypy, which was higher in the small-task condition for one participant. Better work-related behavior occurred for these participants in small- than in large-task conditions even though no tangible reinforcement was provided for task responding. Implications of these results are discussed in the context of arranging workplace environments to maximize productivity of persons with developmental disabilities.

Characterization of two chromosome 12 cosmid libraries and development of STSs from cosmids mapped by FISH.

We have constructed and characterized two related human chromosome 12-specific cosmid libraries. DNA from flow-sorted chromosomes from a somatic cell hybrid was cloned into a cosmid vector. Approximately 61% of the cosmids in the nearly 26,200 member arrayed libraries (LL12NC01 and LL12NC02) contain human DNA inserts, and 31% of the cosmids derived from human DNA contain CA repeats. One hundred and fifty-two cosmids isolated from the libraries have been mapped by fluorescence in situ hybridization (FISH). Cosmids containing human DNA inserts were localized by FISH exclusively to chromosome 12, confirming the chromosomal specificity of the libraries. The cosmids have been localized to all parts of this chromosome, although some regions are more highly represented than others. Partial sequence information was obtained from 44 mapped cosmids, and oligonucleotide primer pairs were synthesized that define unique sequence tagged sites (STSs). These mapped cosmids, and unique STSs derived from them, provide a set of useful clones and primer pairs for screening YAC libraries and developing contigs centered on regions of interest within chromosome 12. In addition, 120 of the mapped cosmids contain CA repeats, and thus they also provide a useful resource for defining highly polymorphic simple tandem repeat elements that serve as genetic markers for linkage analysis and disease gene localization.

Sea urchin small RNA ribonucleoprotein particles: identification, synthesis, and subcellular localization during early embryonic development.

Small RNAs in sea urchins were examined in order to characterize developmental changes in their level, subcellular localization, synthesis, and association with proteins and other RNAs. Small RNAs such as the U snRNAs, 5S and 5.8S rRNAs, and 7S RNAs were identified by their mobility on highly cross-linked acrylamide gels. In addition, 7SL and U1 RNAs were identified by northern blot hybridization to cloned human and sea urchin probes, respectively. The level, subcellular localization, and association with proteins or RNA do not change for most small RNAs from fertilization to blastula, even though this is the time when the stored maternal pool of many small RNAs is being supplemented and replaced by embryonically synthesized RNAs. New embryonic synthesis of small RNAs was first detected at the 8-12 hr blastula stage. Although the predicted subsets of the total small RNA pool can be found in the appropriate subcellular compartments, newly synthesized small RNAs have a predominantly cytoplasmic localization: All of the newly synthesized small RNAs were found to be constituents of small RNPs. The RNPs containing newly synthesized small RNAs had sedimentation rates indistinguishable from their maternal counterparts. Thus, on the basis of sedimentation rate, no gross differences could be detected between maternal and embryonic small RNP pools. These small RNPs include a cytoplasmic RNP containing newly synthesized U1 snRNA and the sea urchin signal recognition particle (SRP) containing the 7SL, RNA. We have also identified a small RNP bearing the 5S rRNA which is present in both eggs and embryos. The presence of multiple, abundant, small RNAs and RNPs that are maintained at constant levels in particular subcellular fractions throughout development suggests that small RNAs may be involved in many more cellular activities than have so far been described.

Characterization of potentially functional 5S rRNA-encoding genes within ribosomal DNA repeats of the nematode Meloidogyne arenaria.

In the plant-parasitic nematode Meloidogyne arenaria, isolated rDNA repeats show length heterogeneity, and are unusual in that they contain putative 5S ribosomal RNA pseudogenes [Vahidi et al., J. Mol. Evol. 27 (1988) 222-227]. Potentially functional 5S rRNA-encoding genes can also be identified in various rDNA repeats, which appear to be tandemly organized in the genome.

The effect of arm position and capsular release on rotator cuff repair. A biomechanical study.

A cadaver study was performed to determine the effect of arm position and capsular release on rotator cuff repair. Artificial defects were made in the rotator cuff to include only the supraspinatus (small) or both supraspinatus and infraspinatus (large). The defects were repaired in a standard manner with the shoulder abducted 30 degrees at the glenohumeral joint. Strain gauges were placed on the lateral cortex of the greater tuberosity and measurements were recorded in 36 different combinations of abduction, flexion/extension, and medial/lateral rotation. Readings were obtained before and after capsular release. With small tears, tension in the repair increased significantly with movement from 30 degrees to 15 degrees of abduction (p < 0.01) but was minimally affected by changes in flexion or rotation. Capsular release significantly reduced the force (p < 0.01) at 0 degree and 15 degrees abduction. For large tears, abduction of 30 degrees or more with lateral rotation and extension consistently produced the lowest values. Capsular release resulted in 30% less force at 0 degree abduction (p < 0.05).

Association of 7 SL RNA and an SRP-like particle with polysomes and endoplasmic reticulum in the developing sea urchin embryo.

We have identified the sea urchin cognate of the mammalian signal recognition particle (SRP). This particle contains the diagnostic 7 SL small RNA, sediments at a similar velocity to that reported for the mammalian particle, and is found associated with the ER and polysomes. We have examined its subcellular localization during embryogenesis in order to determine whether it could serve in a translational regulatory capacity for a subset of the stored maternal mRNAs. In these studies the 7 SL RNA was used as a marker for the particle, since we determined that the 7 SL RNA exists exclusively within the SRP-like particle at all developmental stages. The relative distribution of the SRP among cytoplasmic structures changes dramatically during development. This represents an actual change in subcellular localization because the 7 SL RNA level remains nearly constant per embryo until the pluteus stage, when it increases slightly. In eggs, the SRP exists almost entirely free in the cytoplasm as an 11 S particle. Very soon after fertilization and throughout development there is an increase in the association of the particle with rapidly sedimenting structures, until by the pluteus stage greater than 90% of the SRP exists in a bound state. The nature of the associations is complex, and the bound structures include, at least in part, ribosomes, polysomes, and microsomes. The SRP is associated with microsomal membranes in gastrula (36 hr) but not in blastula (12 hr) or earlier embryos. Using the criteria of sensitivity to Triton X-100, we determined that 16% of the SRP in a 10,000g cytoplasmic fraction was bound to membranes in a microsomal (endoplasmic reticulum)-containing fraction in the gastrula. In contrast, less than 1% was membrane associated in the blastula. The SRP was also found in a ribosome-polysome fraction in 12-, 36-, and 48-hr embryos, but not in eggs. Finally, a small but significant portion of the SRP was found associated with monosomes in cleavage stage embryos. The possible role the SRP could play in the elongation arrest of stored maternal messages for secreted proteins is discussed.

Patellar complications in total knee arthroplasty. A literature review.

Increased implant longevity, improved range of motion, and the use of total knee arthroplasty in younger and more active patients have placed greater demands on the patella component. Commonly observed complications of the patellofemoral joint are crepitation, subluxation, excessive wear, loosening, and persistent patient discomfort. These complications have been attributed to inadequate prosthetic design, fixation techniques, anatomic abnormalities, and surgical error. This paper reviews the most prevalent complications and discusses their causes and prevention.

Stimulus equalization: temporary reduction of stimulus complexity to facilitate discrimination learning.

Learners with limited behavioral repertoires often have difficulty discriminating complex, multidimensional stimuli. Procedures that use gradual stimulus change have been developed to facilitate such discrimination, but these procedures are often difficult to implement and costly in terms of teacher time and expertise. This study investigated the effectiveness of stimulus equalization, an error reduction procedure involving an abrupt but temporary reduction of dimensional complexity. A microcomputer was used for stimulus presentation, data collection, and response analyses. Preschool children's responding to groups of four stimuli differing along several dimensions was analyzed on four discrimination tasks under several conditions. On each task, one element from a different dimension was programmed as correct. When trial-and-error training failed to establish the discrimination, equalization training began in which differences in the irrelevant dimensions were eliminated. When correct responding developed, the differences were reinstated, and correct performance was maintained in all but one instance. In a repeated acquisition design, stimulus equalization was found to be generally effective and superior to the trial-and-error method. Implications for computer-assisted instruction are discussed.

Germination, respiration, and adenylate energy charge of seeds at various oxygen partial pressures.

The effect of O(2) partial pressure on the germination and the respiration of 12 cultivated species was studied. The reciprocal of the time necessary to observe rootlet emergence in 50% of the seeds was used to approach the germination rate. The maximum germination and respiration rates were reached in most seeds at O(2) pressures close to that of air. Decreasing the O(2) pressure produced a gradual decrease of the germination rate. The seeds could be classed in two groups according to their response to low O(2) pressures. Group I includes lettuce, sunflower, radish, turnip, cabbage, flax, and soybean: at O(2) pressures close to 2 kilopascals, the germination in this group was stopped and the adenylate energy charge was lower than 0.6. Group II includes rice, wheat, maize, sorghum, and pea. The germination rate of these seeds was also gradually decreased by lowering the O(2) partial pressure but germination still occured, very slowly, at 0.1 kilopascal; the adenylate energy charge remained higher than 0.6. These differences in the germination rates and adenylate energy charge values could not be explained by differences in the sensitivity of respiration to O(2).

The simplest treatment alternative: the law of parsimony applied to choosing appropriate instructional control and errorless-learning procedures for the difficult-to-teach child.

A method for choosing effective teaching procedures for difficult-to-teach children is proposed. Assessment of child responses during teaching that involves gradually increasing environmental support in the learning setting is the basis for choice. The levels of environmental support in which child responses are assessed are (1) trial-and-error procedures; (2) increased environmental support involving analyses of reinforcement systems, incompatible responses, and prerequisite skills, as well as the most effective use of instructional control; and (3) errorless-learning procedures. Effects of instructions upon learning are discussed in terms of instructional detail and pacing, as well as with respect to the role of instructions in feedback and progressively delayed cue procedures. Stimulus shaping and stimulus fading are discussed in terms of the effectiveness of each for teaching children who have difficulty learning with more traditional procedures. The importance of the incorporation of criterion-related cues when utilizing stimulus shaping or fading is emphasized. It is proposed that an assessment of child responses should be made with respect to the three general levels of environmental support, as well as from sublevels within these, in order to choose the simplest but still effective alternative procedure for teaching difficult-to-teach children.

Conditional discrimination after errorless and trial-and-error training.

Children were trained on a visual discrimination by stimulus shaping, stimulus fading, or trial-and-error. Those who did not acquire the conditional discrimination received a second, different training. More children initially trained by stimulus shaping acquired the conditional discrimination than did those initially trained with stimulus fading or trial-and-error. After a history of fading or trial-and-error training, children were less likely to acquire the conditional discrimination even after the more successful procedure of shaping was later used.

Functional considerations in the use of procedural timeout and in effective alternative.

Two single-subject experiments were conducted with students in special preschool classes. In Experiment I, the subject's disruptive, appropriate, and inappropriate play behaviors were measured as a function of three independent variables: reinforcement, a typical timeout procedure, and regularly paced teacher instructions. In an ABA reversal within a multiple baseline across two teachers, all three independent variables comprised the A conditions and procedural timeout was omitted in B. Experiment II examined a second subject's appropriate and inappropriate eating as a function of the same three variables. Two teachers conducted baseline and paced instruction-plus-reinforcement conditions in multiple baseline across teachers. Subsequently, one teacher performed a series of reversals and replications with various combinations of a typical timeout procedure and reinforcement mixed with paced instructions. The results of both experiments suggest that timeout did not produce response decrement in a punishment paradigm, but rather produced response increment in a negative reinforcement paradigm. These results prevailed, even though a reinforcer was operating in the environment before introducing timeout. Paced instructions (delivering instructions to the child at a set pace regardless of the child's behavior) appears to be an alternative when timeout is not effective and, in conjunction with reinforcement, was demonstrated to reduce inappropriate behavior to near zero.

Implications of the stereotyping and modification of sex role.

This article discusses and questions a study by Rekers and Lovaas (1974), which sought to "normalize" a young boy's sex-role behavior. The reasons given for treatment and the treatment itself are questioned. The ethical implications of the treatment and its outcome are then discussed, and alternative treatment procedures are suggested. Finally, the experimenters' description of the feminine sex-role is criticized.

Differential reinforcement of other behavior and noncontingent reinforcement as control procedures during the modification of a preschooler's compliance.

Differential reinforcement of other behavior (DRO) and noncontingent reinforcement were compared as control procedures during the modification of a 3-yr-old preschooler's compliance. The recorded reinforcer was teacher proximity (within 3 ft (0.9) of the subject for at least 5 sec) which was often accompanied by positive verbal comments that varied in content across experimental conditions. The verabal content during contingent reinforcement might have been: "Thank you for picking up the blocks"; during non-contingent reinforcement: "You're wearing a pretty dress"; and during DRO: "I don't blame you for not picking up because it isn't any fun". Contingent reinforcement increased compliance in all manipulation conditions. Noncontingent reinforcement decreased compliance during two reversal conditions. However, the behavior was variable and did not decrease to the low levels reached during the two DRO reversals.