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R Parker

Publications and source records attributed to R Parker.

At least 181 records · Page 10Linked to original sources
PubMed1988

Analysis of mutant frequency curves and survival curves applied to the AL hybrid cell system.

A model is presented for the statistical analysis of survival curves and mutant frequency curves for a hybrid cell system. The derivation of the model is given in the Appendix, and depends on simple assumptions about the distribution of insults, their repair, and the loss of a marker that is not rescued. A single formula (5) is found which relates a survival curve to the mutant frequency curve, i. e., the response curve for production of mutants per 10(5) survivors induced by a mutagen. The analysis is applied to loss of the a1 gene in AL-J1 hybrid cells submitted to Cesium gamma-rays. Previous experimental data using X-rays was reported by Waldren et al. (1986: Proc. Natl. Acad. Sci, USA 83, 4839.) Also, a derived formula (10), which predicts the probability that in a surviving cell a marker is lost and not rescued, will form the basis for testing the validity of the model in the future using new experimental data.

Analysis of Variance↗
PubMed1988

Orientation-dependent function of a short CYC1 DNA fragment in directing mRNA 3' end formation in yeast.

We have cloned an 82-base-pair region spanning the site of normal 3' end formation of Saccharomyces cerevisiae CYC1 mRNA into an integrative vector carrying the 5' end of the actin gene (including its intron) fused in frame to HIS4ABC sequences. This vector can confer the ability to grow on histidinol if HIS4C (encoding histidinol dehydrogenase) is sufficiently expressed. With the CYC1 fragment cloned in its wild-type (forward) orientation within the actin intron, transformants cannot grow on histidinol, whereas cells transformed with the vector carrying the reverse orientation of this fragment are able to grow well. RNA transfers demonstrate that transformants containing the forward orientation accumulate less than 40% of the control level of full-length mRNA and reveal the presence of a short, stable (approximately equal to 300 nucleotides) poly(A) RNA that represents 60-70% of the transcripts originating from the same promoter. The reverse orientation of the insert allows near-normal levels of full-length mRNA. Mapping of the 3' end of the truncated RNA indicates that poly(A) addition is variable in length but occurs at the same location as in the normal CYC1 transcript. Dominant and recessive suppressor mutations permit growth on histidinol despite the inserted fragment. Genetic analyses indicate that most of the dominant mutants are cis-acting and that the recessive mutants define a minimum of three complementation groups, indicating that defects in several different genes can restore higher levels of HIS4C expression.

Actins↗
PubMed1988

Genetic analysis of small nuclear RNAs in Saccharomyces cerevisiae: viable sextuple mutant.

Saccharomyces cerevisiae contains at least 24 distinct small nuclear RNAs (snRNAs), several of which are known to be essential for viability and to participate in the splicing of pre-mRNAs; the RNAs in this subset contain binding sites for the Sm antigen, a hallmark of metazoan snRNAs involved in mRNA processing. In contrast, we showed previously that the single-copy genes for three other snRNAs (snR3, snR4, and snR10) are not required for viability, although cells lacking snR10 are growth impaired at low temperature. None of these RNAs associates with the Sm antigen. To assess this apparent correlation, we cloned and sequenced the genes encoding three additional non-Sm snRNAs. Comparison of these genes with nine additional yeast snRNA genes revealed a highly conserved TATA box located 92 +/- 8 nucleotides 5' of the transcriptional start site. By using the technique of gene replacement with null alleles, each of these three single copy genes was shown to be completely dispensable. We constructed multiple mutants to test the hypothesis that, individually, each of these snRNAs is nonessential because the snRNAs play functionally overlapping roles. A mutant lacking five snRNAs (snR3, snR4, snR5, snR8, snR9) was indistinguishable from the wild type, and growth of the sextuple mutant was no more impaired than that in strains lacking only snR10. This widespread dispensability of snRNAs was completely unexpected and forces us to reconsider the possible roles of these ubiquitous RNAs.

Base Sequence↗
PubMed1987

Survival with the acquired immunodeficiency syndrome. Experience with 5833 cases in New York City.

In a cohort of 5833 subjects in whom the acquired immunodeficiency syndrome (AIDS) was diagnosed in New York City before 1986, the cumulative probability of survival (mean +/- SE) was 48.8 +/- 0.7 percent at one year and 15.2 +/- 1.8 percent at five years. The group with the most favorable survival rate--white homosexual men 30 to 34 years old who presented with Kaposi's sarcoma only--had a one-year cumulative probability of survival of 80.5 percent; that group was used as the reference group in assessing the effect of five variables: sex, race or ethnic background, age, probable route of acquiring AIDS (risk group), and manifestations of AIDS at diagnosis. The range in the mortality rate was greater than threefold, depending on these variables. Black women who acquired the disease through intravenous drug abuse, for example, had a particularly poor prognosis. The manifestations of disease at diagnosis had the most influence on survival, accounting on average for 56.3 percent of the excess risk. This variable was followed in importance by age (12.2 percent), race or ethnicity (10.6 percent), risk group (8.4 percent), and sex (8.0 percent), with 4.5 percent of the risk attributable to interactions between variables. When we compared subcohorts based on the year of diagnosis (1981 through 1985), we found a significant improvement in the one-year cumulative probability of survival among subjects with Pneumocystis carinii pneumonia, but not among subjects without P. carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Serial acquisition of data to predict one-year mortality rate after acute myocardial infarction.

Eight hundred sixty-six patients with acute myocardial infarction (AMI) were enrolled in a prospective study to determine optimal predictors of long-term prognosis. During 12-month (mean) follow-up there were 65 cardiac deaths and 21 nonfatal repeat AMIs. Twenty-nine variables (from the history, physical examination, serum chemistries, ambulatory monitor, radionuclide ventriculogram and exercise test) were arranged into in 5 sequential groups according to the time at which results became available during hospitalization. Multivariate analysis (logistic regression) and receiver-operator characteristic curves were used to assess improvement in prediction of mortality or repeat AMI by addition of each group of variables. The first group of independent predictors included rales, left bundle branch block and symptom status at 1 month before admission. Addition of information from ambulatory monitoring or serum chemistry did not improve prediction. Radionuclide ejection fraction made a statistically significant, independent contribution to mortality prediction. Of the final group the only exercise test variable that contributed independently to prediction was whether the patients took the test. However, receiver-operator characteristic curves showed that improvement in sensitivity and specificity by addition of information from the radionuclide scan and exercise test was clinically insignificant. Our results imply that costly tests after AMI should be reserved for specific indications and not applied universally for prognosis. Although these tests were highly predictive individually, each test generally added little to preexisting prognostic information.

Follow-Up Studies↗
PubMed1987

Recognition of the TACTAAC box during mRNA splicing in yeast involves base pairing to the U2-like snRNA.

The U2 snRNP binds to the site of branch formation during splicing of mammalian pre-mRNA in vitro. In Saccharomyces cerevisiae the branch site is within the so-called TACTAAC box (UACUAAC box), an absolutely conserved intron sequence required for splicing. Based on the identification and sequence of a U2 analogue in yeast, a specific base pairing interaction between the UACUAAC box and a highly conserved region of this snRNA can be proposed. To test this hypothesis, we have taken advantage of two mutations constructed previously in the UACUAAC box of an actin-HIS4 fusion. These mutant strains were transformed with stable plasmids bearing U2-like snRNAs into which changes predicted to restore base pairing had been introduced. Allele-specific suppression of biological and biochemical phenotypes was observed in both cases. Recognition of the UACUAAC box thus relies, at least in part, on Watson-Crick base pairing with the yeast U2 analogue.

Alleles↗
PubMed1987

Pattern-recognition program for analysis of colon myoelectric and pressure data.

A pattern-recognition program was developed which emulates visual scoring of colonic myoelectric and pressure recordings. It smoothes digitized data with a moving average filter, computes difference scores between successive groups of three data points, and uses the signs of these difference scores to detect the beginning and end of waves. Adjacent waves are merged if their means are closer than 1.67 times the sum of their standard deviations, and amplitude and duration criteria are used to exclude nonsignificant waves. When compared to four experienced human scorers on randomly selected records, the program agreed as well with the human scorers as they agreed with each other, and it approached the level of agreement of these observers with themselves when they were asked to rescore the same records blindly four to six weeks later. Human scorers agreed with themselves on 36-71% of myoelectric slow waves and on 42-88% of pressure waves, compared to 100% test-retest reliability for the pattern-recognition program. Frequency histograms of the duration of waves detected by the pattern-recognition program differed from the spectra generated by the fast Fourier transform (FFT) method. This pattern-recognition program provides an alternative to spectral analysis for the reliable and objective quantification of colonic myoelectric slow waves and pressure waves.

Algorithms↗
PubMed1987

A role for aromatizable androgens in female rat puberty.

The function that aromatizable androgens may have in female puberty is unclear. The present experiments were undertaken to examine, using a quantitative approach, the role that physiological levels of these androgens may play in determining the timing of vaginal opening and first ovulation in female rats. Serum androstenedione (delta 4) levels increased markedly between Postnatal Days 4 and 8, remained elevated through Day 16, and declined thereafter to remain at about 100 pg/ml throughout juvenile development (Days 20-32). Serum testosterone (T) also increased, though less prominently after Postnatal Day 4. Maximal values were found at Day 12 (about 150 pg/ml); thereafter, T levels decreased to intermediate values (about 100 pg/ml), which were maintained during juvenile days. Serum dehydroepiandrosterone (DHA) remained undetectable throughout prepubertal development. At puberty, serum delta 4 increased 2.5-fold, but only at the time of the preovulatory luteinizing hormone (LH) surge. In contrast, T levels increased significantly 2-fold on the early proestrous-2 phase of puberty, 3.5-fold on the morning of first proestrus, and 9-fold at the time of the LH surge. Serum DHA remained undetectable. Implantation of Silastic capsules containing T at 2 or 6 mg/ml oil into juvenile 28-day-old rats resulted in serum T levels similar to those found on early proestrous 2 (about 150-180 pg/ml) and at 1300 h of first proestrus (ca. 300-400 pg/ml), respectively. Both treatments induced precocious vaginal opening, but failed to advance first ovulation. About 50% of the T-implanted rats had ambiguous estrous-type vaginal cytology preceding the day of first diestrus, and failed to show corpora lutea at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1987

A trans-acting suppressor restores splicing of a yeast intron with a branch point mutation.

Splicing of introns from Saccharomyces cerevisiae pre-mRNA requires the conserved sequence TACTAAC; the 3'-most A residue is utilized as the site of branch formation. We showed previously that the transcript from an actin-HIS4 gene fusion containing the mutation TACTAAC to TACTACC (designated C259) is spliced inefficiently, thereby preventing growth on the histidine precursor histidinol. By selecting for growth on histidinol, we have identified a mutant in which the splicing of the C259 transcript is increased fourfold; splicing of other mutated introns is not significantly improved. The mutant locus encodes a trans-acting suppressor. A single mutation, rna16-1, is sufficient for suppression; however, suppression is maximized in heterozygous diploids containing both rna16-1 and the wild-type allele RNA16. In addition, wild-type pre-mRNAs (and lariat intermediates) accumulate in rna16-1 cells. We propose that the RNA16 locus encodes a component of the splicing machinery.

Genes, Fungal↗
PubMed1987

Viability and morphology of aortic and pulmonary homografts. A comparative study.

In view of possible clinical use of the pulmonary homograft for right ventricular outflow tract reconstruction a comparative study with the aortic counterpart was performed. Samples of aortic and pulmonary walls from 10 cadaveric hearts were assessed for viability and morphologic characteristics before and after storage in nutrient-antibiotic solution. The viability, as evaluated by an autoradiographic technique, was similar in both aortic and pulmonary specimens at the time of dissection, after 2 weeks, and after 4 weeks of storage. The histologic examination showed no changes in the structure of the media in all samples up to 4 weeks of storage. The total calcium content per gram of tissue in the pulmonary media was on an average less than half of that in the aortic counterpart. We conclude that the pulmonary homograft is preserved the same as the aortic homograft and, accordingly, it becomes available for clinical application. Moreover, a lesser content of elastic tissue and a lower amount of total calcium may, in all likelihood, make the pulmonary wall less prone to calcification.

Adolescent↗
PubMed1986

Chemotherapy of synovial cell sarcoma in a dog.

A synovial cell sarcoma of the tarsus in a 6-year-old dog was treated with doxorubicin HCl and cyclophosphamide. The tumor regressed after treatment. There was no recurrence 3 years after initiation of treatment. Previously, synovial cell sarcoma has not been reported to be responsive to chemotherapeutic agents, and the treatment of choice has been amputation.

Animals↗
PubMed1986

Mutations in conserved intron sequences affect multiple steps in the yeast splicing pathway, particularly assembly of the spliceosome.

Yeast introns contain three highly conserved sequences which are known to be required for splicing of pre-mRNA. Using in vitro mutagenesis, we have synthesized seven point mutations at five different sites in these signals in the yeast actin intron. The mutant introns were then inserted into each of three constructs, which allowed us to assess the consequences both in vivo and in vitro. In virtually every case, we found the efficiency of splicing to be significantly depressed; mature mRNA levels in vivo ranged from 0 to 47% of wild-type. Surprisingly, the tightest mutations were not necessarily at the sites of nucleolytic cleavage and branch formation; these nucleotides are thus highly preferred, but are not absolutely necessary. Moreover, while particular nucleotides are specifically required for the final step in splicing, i.e. 3' cleavage and exon ligation, the predominant consequence of mutation within the conserved signals appears to be the inhibition of assembly of the splicing complex.

Actins↗
PubMed1986

European vestibular experiments on the Spacelab-1 mission: 3. Caloric nystagmus in microgravity.

Response to caloric stimulation was examined in two subjects in the weightless environment of orbital flight. Using air insufflation, a binaural temperature stimulus profile was performed twice on each subject during flight. In all but one test, which was carried out on the first mission day, a caloric nystagmus was registered. This zero-g nystagmus was similar to ground-based pre- and postflight responses with regard to its intensity, its temporal correlation with the stimulus profile (nystagmus was always directed towards the warmer ear) and the subjective sensations reported by the tested subjects. These findings demonstrate that mechanisms other than thermoconvection are involved in the elicitation of the caloric nystagmus response. At each stage of the temperature stimulus profile, linear acceleratory stimulation was presented in the form of oscillations in the X-axis. Some differences were found between one-g and zero-g conditions in the resultant modification of the nystagmus response.

Caloric Tests↗
PubMed1986

Management of carcinoma of the rectum and anus without abdominoperineal resection.

Since 1979, 16 patients with cancer of the rectum and anus have been treated without abdominoperineal resection. All have received radiotherapy. Nine of these had local excision before receiving radiotherapy. There has been no evidence of recurrent cancer in 15 of the 16 patients with a median follow-up period of 24 months (range 14 to 52 months) for a recurrence rate of 6 percent. We conclude that limited excision, radiotherapy, or both are viable alternatives to abdominoperineal resection of small, early cancers of the rectum and anus.

Adenocarcinoma↗
PubMed1986

Activation of a cryptic TACTAAC box in the Saccharomyces cerevisiae actin intron.

We constructed a translational fusion between the Saccharomyces cerevisiae actin gene and the Escherichia coli beta-galactosidase structural gene such that expression of beta-galactosidase activity required accurate splicing of the actin intron. Using this chimeric gene, we generated a series of internal deletions which removed the TACTAAC box or, in addition, TACTAAC-like sequences within the intron. Analysis of the fusion transcripts produced in these deletions allowed us to conclude that the TACTAAC-like sequence TACTAAG can substitute, albeit inefficiently, for the authentic TACTAAC box in the splicing process. These results indicate that the yeast splicing machinery can utilize a cryptic TACTAAC box, but there are requirements for primary sequence and proper position.

Actins↗
PubMed1986

Measurement technology applications in performance appraisal.

Every nursing administrator needs a credible performance appraisal system. By using psychometric methods and computer technology, the process of developing such a system can be more efficient and demonstrably successful. This article raises issues that relate to changing the performance appraisal system and gives a clear, step-by-step description of how computerized, statistical procedures were applied in improving nursing performance appraisal.

Computers↗