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Biomedical subjects

A Jacobson

Publications and source records attributed to A Jacobson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae.

We developed a procedure to measure mRNA decay rates in the yeast Saccharomyces cerevisiae and applied it to the determination of half-lives for 20 mRNAs encoded by well-characterized genes. The procedure utilizes Northern (RNA) or dot blotting to quantitate the levels of individual mRNAs after thermal inactivation of RNA polymerase II in an rpb1-1 temperature-sensitive mutant. We compared the results of this procedure with results obtained by two other procedures (approach to steady-state labeling and inhibition of transcription with Thiolutin) and also evaluated whether heat shock alter mRNA decay rates. We found that there are no significant differences in the mRNA decay rates measured in heat-shocked and non-heat-shocked cells and that, for most mRNAs, different procedures yield comparable relative decay rates. Of the 20 mRNAs studied, 11, including those encoded by HIS3, STE2, STE3, and MAT alpha 1, were unstable (t1/2 less than 7 min) and 4, including those encoded by ACT1 and PGK1, were stable (t1/2 greater than 25 min). We have begun to assess the basis and significance of such differences in the decay rates of these two classes of mRNA. Our results indicate that (i) stable and unstable mRNAs do not differ significantly in their poly(A) metabolism; (ii) deadenylation does not destabilize stable mRNAs; (iii) there is no correlation between mRNA decay rate and mRNA size; (iv) the degradation of both stable and unstable mRNAs depends on concomitant translational elongation; and (v) the percentage of rare codons present in most unstable mRNAs is significantly higher than in stable mRNAs.

Blotting, Northern↗
PubMed1990

mRNA poly(A) tail, a 3' enhancer of translational initiation.

To evaluate the hypothesis that the 3' poly(A) tract of mRNA plays a role in translational initiation, we constructed derivatives of pSP65 which direct the in vitro synthesis of mRNAs with different poly(A) tail lengths and compared, in reticulocyte extracts, the relative efficiencies with which such mRNAs were translated, degraded, recruited into polysomes, and assembled into messenger ribonucleoproteins or intermediates in the translational initiation pathway. Relative to mRNAs which were polyadenylated, we found that nonpolyadenylated [poly(A)-]mRNAs had a reduced translational capacity which was not due to an increase in their decay rates, but was attributable to a reduction in their efficiency of recruitment into polysomes. The defect in poly(A)- mRNAs affected a late step in translational initiation, was distinct from the phenotype associated with cap-deficient mRNAs, and resulted in a reduced ability to form 80S initiation complexes. Moreover, poly(A) added in trans inhibited translation from capped polyadenylated mRNAs but stimulated translation from capped poly(A)- mRNAs. We suggest that the presence of a 3' poly(A) tail may facilitate the binding of an initiation factor or ribosomal subunit at the mRNA 5' end.

Animals↗
PubMed1990

The relevance of childhood sexual abuse to adult psychiatric inpatient care.

The prevalence and characteristics of childhood sexual abuse among 50 male and 50 female psychiatric inpatients were assessed in direct interviews. Forty patients reported some type of childhood sexual abuse. Abuse involving genital contact was reported by one in six men inpatients and one in five women and was often recurrent. Forty-four percent of patients who had experienced serious abuse had not revealed it to anyone, including prior therapists. Patients often reported that the abuse experiences continued to affect their current functioning. In clinical assessments, routine inquiry about childhood sexual abuse appears justified to clarify diagnoses and establish effective treatment plans. The authors make specific recommendations for a brief, routine clinical assessment for history of childhood sexual abuse.

Adolescent↗
PubMed1990

Planning for orthognathic surgery--art or science?

Computerization and sophisticated radiographic and nonradiographic technology in orthodontics and orthognathic surgery have contributed immensely to the stockpile of knowledge. Yet, in spite of the tremendous technological and scientific advances in these areas, the question of whether treatment planning for orthognathic surgery is an art or a science continues to loom in the minds of clinicians. All too frequently, "scientific" observations do not corroborate clinical findings. The extent to which clinicians are able to rely on current technology is directly dependent on their understanding of its shortcomings. This article examines the limitations of modern technology in clinical diagnosis.

Cephalometry↗
PubMed1989

Evaluation of aluminum-yttrium filtration for intraoral radiography.

In comparison with the use of traditional aluminum filtration, a radiation dose reduction of 40% at 90 kVp and 25% at 70 kVp was found with the use of aluminum-yttrium (Al-Y) filtration for intraoral bitewing and periapical radiographs. An increased exposure time, and consequent greater tube loading, was necessary to maintain film density. Extended gray-scales (i.e., reduced radiographic contrast) occurred at both energy levels tested with the use of Al-Y filtration. Subjective evaluation of image quality in terms of clarity, resolution, and contrast was carried out independently by nine periodontologists. Despite some interoperator variance, there was a preponderant preference for traditional aluminum filtration.

Aluminum↗
PubMed1989

Physical and sexual assault histories among psychiatric outpatients.

Using a semistructured interview, the author obtained complete histories of experiences of being physically or sexually assaulted from 31 psychiatric outpatients. The majority (68%) of outpatients had experienced major physical and/or sexual assaults, and most assaults had not been revealed to the patients' prior therapists. Circumstances associated with the assaults, a comparison of outpatient and inpatient assault histories, and the relevance of the findings to clinical practice are discussed.

Adult↗
PubMed1989

Prospective study of a standardized questionnaire to improve clinical estimate of pulmonary embolism.

A standardized questionnaire was administered to 100 patients suspected of having pulmonary embolism to investigate whether clinical data may be reliably used in the decision-making process of such patients. Questionnaire data were compared with lung scintigraphy outcome and 16 variables were selected as significantly associated with the scintigraphic diagnosis. Based on these variables, patients with abnormal scintigraphy compatible with pulmonary embolism and patients with scintigraphy not compatible with embolism were classified in accordance with the scintigraphic diagnosis. When these 16 variables were tested in an additional validation group, clinical and scintigraphic diagnosis matched in most cases. These results show that clinical data can be used to predict the outcome of lung perfusion scintigraphy in patients suspected of pulmonary embolism. Use of a standardized questionnaire can improve the accuracy of pretest assessment of such patients and positively influence the decisions to start heparin coverage or obtain pulmonary angiography.

Electrocardiography↗
PubMed1989

Short-term and long-term soft tissue profile changes after mandibular advancements using rigid fixation techniques.

This study was designed to describe short- and long-term soft tissue profile changes that follow surgical advancement of the mandible, to provide a database for prediction of facial changes following surgery. A number of hard and soft tissue landmarks were identified on serial cephalometric tracings of 31 patients. The long-term data (x = 14.0 months postsurgery) showed that changes in soft tissue landmarks overlying the skeletal structures followed their hard tissue counterpart in a 1:1 ratio in the horizontal direction. Horizontal hard to soft tissue landmark changes between mandibular incisor and lower lip, however, were found to be different; the average ratio was 0.43:1.00. Short-term data (x = 2.7 months postsurgery) showed soft tissue changes to be stable when compared to long-term changes.

Adolescent↗
PubMed1988

Regulation of mRNA stability and the poly(A) problem in Dictyostelium discoideum.

This paper reviews our studies of three aspects of post-transcriptional regulation in Dictyostelium discoideum: 1) the determinants of mRNA stability in vegetative amoebae; 2) the effects of disaggregation and cyclic AMP on the decay rates of cell-type-specific mRNAs in late developing cells; and 3) the cytoplasmic function of the 3' poly(A) tracts present on most mRNAs. We find that: 1) mRNA stability in vegetative amoebae is not dependent on mRNA size, ribosome loading, or poly(A) tract length, but may be determined by specific 3'-untranslated sequences within a given mRNA; 2) mRNA decay rates in late developing cells are heterogeneous, and cyclic AMP does not act directly to stabilize cell-type-specific mRNAs; and 3) poly(A) is most likely involved in the initiation of protein synthesis via an interaction with cytoplasmic poly(A)-binding proteins.

Dictyostelium↗
PubMed1988

Post-transcriptional regulation of ribosomal protein gene expression during development in Dictyostelium discoideum.

We have isolated recombinant plasmids that contain cDNA inserts complementary to mRNAs encoding six different r-proteins of Dictyostelium discoideum. Southern and quantitative dot blot analyses have shown that each of the r-protein genes represented in these plasmids is encoded by a single copy gene and that these genes are not tightly linked to each other. We have determined the relative amount of the six r-protein mRNAs present in cells at intervals throughout development and find that for the first 9 hours of development, each of the mRNAs remains present at virtually the same level as in vegetatively growing cells. Between 9 and 11 hours of development, there is a rapid loss of these mRNAs to 15% or less of vegetative levels, and that low level remains, or slightly declines, through the late stages of development. We have shown that two post-transcriptional events contribute to the developmental regulation of the expression of the r-protein genes. The first involves a specific block to translational initiation that is not the result of inactivation of these mRNAs by decapping or deadenylation. The second is a change in the stability of these mRNAs during early development. In order to begin to analyze the role of specific sequences that may act as targets or signals in these events, we have cloned and sequenced a 1.9-kb genomic DNA fragment that encodes one of the r-proteins. We find that transcription of this gene begins in a pyrimidine-rich region that is not preceded by a TATA box, the gene contains a single intron of 350 bp, and there are two alternative 3' processing sites. In addition, the 5'-untranslated region of the transcript contains an unusually high percentage of G and C residues relative to other Dictyostelium mRNAs.

Amino Acid Sequence↗
PubMed1988

Update on the Wits appraisal.

A review of various aspects of the application of the Wits appraisal of anteroposterior apical base relationships since its introduction in 1975.

Cephalometry↗
PubMed1988

mRNA decay rates in late-developing Dictyostelium discoideum cells are heterogeneous, and cyclic AMP does not act directly to stabilize cell-type-specific mRNAs.

We reevaluated the use of 32PO4 pulse-chases for analyzing mRNA decay rates in late-developing Dictyostelium cells. We found that completely effective PO4 chases could not be obtained in developing cells and that, as a consequence, the decay rates exhibited by some mRNAs were influenced by the rates at which they were transcribed. In developing cells disaggregated in the presence of cyclic AMP, the poly(A)+ mRNA population turned over with an apparent half-life of 4 h, individual mRNA decay rates were heterogeneous, and some prestalk and prespore mRNAs appeared to decay with biphasic kinetics. In cells disaggregated in the absence of cyclic AMP, all prestalk and prespore mRNAs decayed with biphasic kinetics. During the first 1 to 1.5 h after disaggregation in the absence of cyclic AMP, the cell-type-specific mRNAs were selectively degraded, decaying with half-lives of 20 to 30 min; thereafter, the residual prestalk and prespore mRNA molecules decayed at rates that were similar to those measured in the presence of cyclic AMP. This short-term labilization of cell-type-specific mRNAs was observed even for those species not requiring cyclic AMP for their accumulation in developing cells. The observation that cell-type specific mRNAs can decay at similar rates in disaggregated cells with or without cyclic AMP indicates that this compound does not act directly to stabilize prestalk and prespore mRNAs during development and that its primary role in the maintenance of cyclic-AMP-dependent mRNAs is likely to be transcriptional.

Cell Aggregation↗
PubMed1988

Determinants of mRNA stability in Dictyostelium discoideum amoebae: differences in poly(A) tail length, ribosome loading, and mRNA size cannot account for the heterogeneity of mRNA decay rates.

As an approach to understanding the structures and mechanisms which determine mRNA decay rates, we have cloned and begun to characterize cDNAs which encode mRNAs representative of the stability extremes in the poly(A)+ RNA population of Dictyostelium discoideum amoebae. The cDNA clones were identified in a screening procedure which was based on the occurrence of poly(A) shortening during mRNA aging. mRNA half-lives were determined by hybridization of poly(A)+ RNA, isolated from cells labeled in a 32PO4 pulse-chase, to dots of excess cloned DNA. Individual mRNAs decayed with unique first-order decay rates ranging from 0.9 to 9.6 h, indicating that the complex decay kinetics of total poly(A)+ RNA in D. discoideum amoebae reflect the sum of the decay rates of individual mRNAs. Using specific probes derived from these cDNA clones, we have compared the sizes, extents of ribosome loading, and poly(A) tail lengths of stable, moderately stable, and unstable mRNAs. We found (i) no correlation between mRNA size and decay rate; (ii) no significant difference in the number of ribosomes per unit length of stable versus unstable mRNAs, and (iii) a general inverse relationship between mRNA decay rates and poly(A) tail lengths. Collectively, these observations indicate that mRNA decay in D. discoideum amoebae cannot be explained in terms of random nucleolytic events. The possibility that specific 3'-structural determinants can confer mRNA instability is suggested by a comparison of the labeling and turnover kinetics of different actin mRNAs. A correlation was observed between the steady-state percentage of a given mRNA found in polysomes and its degree of instability; i.e., unstable mRNAs were more efficiently recruited into polysomes than stable mRNAs. Since stable mRNAs are, on average, "older" than unstable mRNAs, this correlation may reflect a translational role for mRNA modifications that change in a time-dependent manner. Our previous studies have demonstrated both a time-dependent shortening and a possible translational role for the 3' poly(A) tracts of mRNA. We suggest, therefore, that the observed differences in the translational efficiency of stable and unstable mRNAs may, in part, be attributable to differences in steady-state poly(A) tail lengths.

DNA↗