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Biomedical subjects

S D Rose

Publications and source records attributed to S D Rose.

At least 37 records · Page 2Linked to original sources

In vitro polyadenylation is stimulated by the presence of an upstream intron.

The majority of vertebrate pre-mRNAs are both spliced and polyadenylated. To investigate the mechanism whereby processing factors recognize last exons containing both splicing and polyadenylation consensus elements, chimeric precursor RNAs containing a single intron and a poly(A) site were constructed and assayed for in vitro splicing and polyadenylation. Chimeric RNAs underwent splicing and polyadenylation. Both reactions occurred in a single RNA. The presence of an intron enhanced the rate of polyadenylation at a downstream poly(A) site. The extent of stimulation varied from two- to fivefold, depending on the magnesium concentration. Maximal stimulation of polyadenylation by an upstream intron required a 3' splice site but not a 5' splice site, suggesting that the structure of the terminal exon was more important than the presence of a complete upstream intron. We suggest that splicing and polyadenylation factors interact to recognize terminal, poly(A) site-containing exons. Such interaction may explain why all known intron-containing eukaryotic pre-mRNAs generate their 3' ends by polyadenylation.

Base Sequence↗

Photo-CIDNP detection of pyrimidine dimer radical cations in anthraquinonesulfonate-sensitized splitting.

Anthraquinone-2-sulfonate (AQS) photosensitizes pyrimidine dimer splitting. Electron abstraction from the dimer is thought to induce dimer splitting, but direct evidence for the existence and intermediacy of dimer radical cations has been lacking. By employing photochemically induced dynamic nuclear polarization, we have found emission signals in the NMR spectra of dimers upon photolysis of dimers in the presence of anthraquinone-2-sulfonate. The two dimers employed were cis, syn-thymine dimer in which the N(1)-positions were linked by a three-carbon bridge and the N(3), N(3')-dimethyl derivative of that compound. The anthraquinone-2-sulfonate sensitized photochemically induced dynamic nuclear polarization spectrum of the methylated derivative exhibited an emission signal from the dimer-C(6) hydrogens. This result implied the existence of a dimer radical cation (mD+.) formed by electron abstraction by excited anthraquinone-2-sulfonate and nuclear spin sorting within a solvent caged radical ion pair [mD+. AQS-.]. Product pyrimidine photochemically induced dynamic nuclear polarization signals were also seen [enhanced absorption by C(6)-hydrogens and emission by C(5)-methyl groups]. Nuclear spin polarization in the product resulted from spin sorting in one or more of its precursors, including mD+. The results support the conclusion that dimer radical cations not only exist but are intermediates in the photosensitized splitting of pyrimidine dimers by anthraquinonesulfonate.

Anthraquinones↗

Solvent dependence of pyrimidine dimer splitting in a covalently linked dimer-indole system.

Cyclobutadipyrimidines (pyrimidine dimers) undergo splitting that is photosensitized by indole derivatives. We have prepared a compound in which a two-carbon linker connects a dimer to an indolyl group. Indolyl fluorescence quenching indicated that the two portions of the molecule interact in the excited state. Intramolecular photosensitization of dimer splitting was remarkably solvent dependent, ranging from phi spl = 0.06 in water to a high value of phi spl = 0.41 in the least polar solvent mixture examined, 1,4-dioxane-isopentane(5 : 95). A derivative with a 5-methoxy substituent on the indolyl ring behaved similarly. These results have been interpreted in terms of electron transfer from the excited indolyl group to the dimer, which would produce a charge-separated species. The dimer anion within such a species could split or undergo back electron transfer. The possibility that back electron transfer is in the Marcus inverted region can be used to rationalize the observed solvent dependence of splitting. In the inverted region, the high driving force of a charge recombination exceeds the reorganization energy of the solvent, which is less for solvents of low polarity than those of high polarity. If this theory is applicable to the hypothetical charge-separated species, a slower back electron transfer, and consequently higher splitting efficiencies, would be expected in solvents of lower polarity. Photolyases may have evolved in which a low polarity active site retards back transfer of an electron and thereby contributes to the efficiency of the enzymatic dimer splitting.

Indoles↗

Coping skill training in groups.

Though similar to traditional group psychotherapy in many respects, a coping skill training approach differs principally in several areas and technically in many more. Coping skill training group therapy tends to employ many concrete intervention strategies to enhance various aspects of process, drawing on ongoing data to evaluate group interaction and individual responses. The approach draws more heavily on cognitive, modeling, reinforcement, and problem-solving procedures to achieve specifically determined goals, and it depends less on interpretive and confrontative methods. The author discusses a wide range of techniques to show the benefits of this approach.

Adaptation, Psychological↗

New evidence for the effectiveness of stress management training in groups.

This study evaluates the effectiveness of a stress management treatment based upon transactional stress and group treatment theory. Treatment components included teaching the cognitive-behavioral skills of relaxation, cognitive restructuring, and assertiveness within a structured small-group setting. Thirty-two symptomatic volunteers were assigned to either a treatment group or a wait-list condition. Treatment consisted of eight, two-hour weekly group sessions. On all dependent measures of stress, the treatment subjects evidenced significant pre- to posttest reductions. Furthermore, on three of the four measures, the treatment subjects evidenced significant pre- to posttest reductions in stress compared to the wait-list subjects.

Adaptation, Psychological↗

Social work and the treatment of chronic pain.

The severity and prevalence of chronic pain is a growing concern for all health care professionals. An outpatient program that offered cognitive-behavioral coping skills training in a group setting was studied as a possible social work treatment for chronic pain patients, and the results were encouraging. Such treatments usually are available only in hospital pain clinics and research centers, which reduce treatment availability to patients in other settings. Social workers could provide services in a wider variety of settings to a large and growing population. As social workers realize the continuous interplay of physical, emotional, and cognitive factors in the experience of pain, they will identify appropriate practice roles for working with chronic pain patients.

Adaptation, Psychological↗

U1 small nuclear ribonucleoproteins are required early during spliceosome assembly.

U1 small nuclear ribonucleoproteins (snRNPs) are required for in vitro splicing of pre-mRNA. Sequences within U1 RNA hybridize to, and thus recognize, 5' splice junctions. We have investigated the mechanism of association of U1 snRNPs with the spliceosome. U1-specific antibodies detected U1 association with precursor RNA early during assembly. Removal of the 5' terminal sequences of U1 RNA by oligo-directed cleavage or removal of U1 snRNPs by immunoprecipitation prior to the addition of precursor RNA depressed the association of all snRNPs with precursor RNA as detected by immunoprecipitation of splicing complexes by either Sm or U1-specific antibodies. Assembly of the spliceosome as monitored by gel electrophoresis was also depressed after cleavage of U1 RNA. The dependency of Sm precipitability of precursor RNA upon the presence of U1 snRNPs suggests that U1 snRNPs participate in the early recognition of substrate RNAs by U2 to U6 snRNPs. Although removal of the 5'-terminal sequences of U1 depressed U1 snRNP association with precursor RNA, it did not eliminate it, suggesting semistable association of U1 snRNPs with the assembling spliceosome in the absence of U1 RNA hybridization. This association was not dependent upon 5' splice junction sequences but was dependent upon 3' intronic sequences, indicating that U1 snRNPs interact with factors recognizing 3' intronic sequences. Mutual dependence of 5' and 3' recognition factors suggests significant snRNP-snRNP communication during early assembly.

Adenoviridae↗

Gonococcal endocarditis: a case series demonstrating modern presentation of an old disease.

Gonococcal endocarditis appeared with striking frequency in the preantibiotic era compared with its surprising rarity today. We present a series of four episodes of gonococcal endocarditis, which presented to our institution in the last 2 years, after no cases in the previous decade. Three episodes involved the aortic valve and required emergency aortic valve replacement. One episode involved the tricuspid valve and was successfully cured with antibiotic infusion alone. Combining our four patients with the available 25 well-documented gonococcal endocarditis cases reported in the English medical literature during the antibiotic era, we demonstrated that the disease incidence may be increasing, that infections more often involve left-sided cardiac structures (particularly the aortic valve), and that the association with a quotidian fever curve, rash and arthritis, and overt gonococcal infection is less common than previously reported. These patients frequently present with fulminant and dramatic valvular insufficiency without immediately positive blood cultures and complete echocardiographic evaluation seems to provide a valuable aid in making a presumptive diagnosis of endocarditis and directing appropriate clinical management.

Adult↗

Enzymatic addition of modified cytosine nucleotides to DNA. Methacrylate polymerization by an azo pyrimidine.

An azo pyrimidine that induces the polymerization of 1-glyceryl methacrylate has been prepared. 1-Glyceryl methacrylate contains substituent glycol groups for binding heavy atoms for subsequent electron microscopic studies. Oxodation of 1-methyl N4-ureidocytosine (compound 1A) with N-bromosuccinimide produced 4-aminocarbonylazo-2-pyrimidinone (compound 2A). This orange compound shows a broad peak (lambda max = 349 nm) in its ultraviolet absorption spectrum. Mixing compound 2A with mildly acidic aqueous solutions of 1-glyceryl methacrylate (pH 3.6) resulted in polymerization of the methacrylate. Under these conditions, the ester 1-glyceryl methacrylate does not hydrolyze appreciably as judged by oxidation of the glycol groups with NaIO4 and spectrophotometric analysis of the HCHO liberated using Schiff's reagent. Attachment of azo nucleotides to the 3'-terminus of DNA was achieved in two steps. First, N4-ureidocytosine deoxynucleotides were enzymatically added to single strand DNA primers using calf thymus terminal deoxynucleotidyl transferase, Co2+, and N4-ureido-2'-deoxycytidine 5'-triphosphate (prepared by the HSO3--catalyzed transamination reaction of dCTP with semicarbazide). Second, these modified nucleotides were oxidized with N-bromosuccinimide to produce DNA that contained azo pyrimidine nucleotides at its 3'-end (azoDNA). Upon adding acid to the azoDNA, the azo nucleotides decomposed. If these nucleotides induce methacrylate polymerization upon decomposition as did compound 2A, it may be possible to mark the location of DNA termini in situ for electron microscopy by attaching heavy atoms to the poly(1-glyceryl methacrylate) formed. Such studies may elucidate the nature and location of the ends of the eukaryotic chromosomal DNA molecule in both chromosomes and interphase nuclei.

Acrylic Resins↗

Cardiac risk factors in patients undergoing noncardiac surgery.

Cardiac risks of noncardiac surgery are associated with some noncardiac risk factors but are primarily a function of the patient's underlying cardiac disease. Elective surgery should only be performed when the patient is in optimal condition--i.e., with no evidence of heart failure, at least 6 months after a previous myocardial infarction, and so forth. Careful monitoring of fluid status should lead to reduced cardiac morbidity and mortality after surgery in these patients.

Anesthesia↗