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J Scott

Publications and source records attributed to J Scott.

At least 307 records · Page 17Linked to original sources
PubMed1993

The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase.

The messenger RNA for apolipoprotein B undergoes a discrete and specific C to U editing of nucleotide 6666. This generates a stop translation codon and defines the carboxyl terminus of apolipoprotein B48. A 27-kDa rat intestinal protein that does not itself edit apolipoprotein B mRNA, but confers editing activity on chick intestinal extracts that do not have intrinsic editing activity, has recently been identified and its cDNA cloned (Teng, B., Burant, C. F., and Davidson, N. O. (1993) Science 260, 1816-1819). Here we show that p27 is homologous in the zinc coordinating region of the active site to cytidine deaminases from Escherichia coli, Bacillus subtilis, yeast, and man and to deoxycytidylate deaminases from T2 and T4 bacteriophages and man. p27 expressed in Xenopus laevis oocyte extracts has cytidine deaminase activity and specifically confers editing activity on chick intestinal extracts. The homologous E. coli cytidine deaminase does not confer editing activity. The zinc-specific chelating agent o-phenanthroline abolishes p27 activity and site-specific apolipoprotein B mRNA editing in rat enterocyte editing extracts. We conclude that p27 is the catalytic subunit of the apolipoprotein B mRNA editing enzyme and is a zinc-containing cytidine deaminase.

APOBEC-1 Deaminase↗
PubMed1993

Reversed-phase high-performance liquid chromatographic method for the quantitation of endogenous folate catabolites in rat urine.

We describe a reversed-phase high-performance liquid chromatographic procedure for the analysis of rat urine for p-aminobenzoylglutamate (pABGlu) and its acetamido derivative (p-acetamidobenzoylglutamate, apABGlu). These two catabolites arise following the in vivo cleavage of the folate molecule at the C-9-N-10 bond. Known quantities of high-specific-activity tritiated forms of the catabolites are added as internal standards to aliquots of rat urine. Following preliminary sample clean-up on C18 Sep-Pak cartridges, including derivatisation in the case of pABGlu, the urinary extracts are quantitated by HPLC. The present assay makes possible for the first time the determination of endogenous folate breakdown in the rat.

4-Aminobenzoic Acid↗
PubMed1993

Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group.

Women with low bone density in the radius or calcaneus are at increased risk of hip fracture. To see whether bone density of the hip measured by dual X-ray absorptiometry is a better predictor of hip fracture than measurements of other bones, we assessed bone density at several sites in 8134 women aged 65 years or more. 65 women had hip fractures during a mean follow-up of 1.8 years. Each SD decrease in femoral neck bone density increased the age-adjusted risk of hip fracture 2.6 times (95% CL 1.9, 3.6). Women with bone density in the lowest quartile had an 8.5-fold greater risk of hip fracture than those in the highest quartile. Bone density of the femoral neck was a better predictor than measurements of the spine (p < 0.0001), radius (p < 0.002), and moderately better than the calcaneus (p = 0.10). Low hip bone density is a stronger predictor of hip fracture than bone density at other sites. Efforts to prevent hip fractures should focus on women with low hip bone density.

Absorptiometry, Photon↗
PubMed1993

Adult immunization with acellular pertussis vaccine.

OBJECTIVE: To evaluate the safety and immunogenicity in adults of several different concentrations of an acellular pertussis vaccine. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Medical center immunization clinic. PARTICIPANTS: One hundred eighteen healthy adult volunteers. INTERVENTIONS: Participants received standard adult tetanus-diphtheria vaccine alone or combined with full-strength, half-strength, or quarter-strength concentrations of a currently licensed acellular pertussis vaccine used for booster doses in young children. Full-strength vaccine contained 40 micrograms of pertussis proteins, consisting of 86% filamentous hemagglutinin, 8% pertussis toxin, 4% 69-kd outer-membrane protein, and 2% agglutinogens. MAIN OUTCOME MEASURES: Local and systemic reactions were assessed for 14 days after vaccination. Serum samples for antibody assay were obtained before, 1 month after, and 1 year after immunization. RESULTS: Adverse reactions were few and minor and did not differ in frequency or severity among the four study groups. The groups receiving acellular pertussis vaccine showed strong antibody responses to pertussis antigens, which did not significantly differ by concentration of vaccine. After 1 year, levels of antibody to pertussis had declined by approximately 50% but remained substantially higher than preimmunization levels. The four groups did not differ in antibody responses to tetanus or diphtheria toxoids. CONCLUSIONS: Routine reimmunization of adults with a vaccine containing acellular pertussis antigens in addition to diphtheria and tetanus toxoids can substantially enhance pertussis antibody levels without an increase in adverse reactions or diminution in response to the diphtheria and tetanus components. Such a program might materially reduce respiratory illness among both adults and children.

Adult↗
PubMed1993

Apolipoprotein B mRNA editing is associated with UV crosslinking of proteins to the editing site.

Apolipoprotein (apo) B100 mRNA undergoes editing of C-6666 to a U residue, which generates a stop-translation codon and defines the carboxyl terminus of apoB48. To aid purification of the editing enzyme we have undertaken UV crosslinking of a 32P-labeled substrate for apoB mRNA editing in vitro to proteins in an enterocyte editing extract. Proteins of 60 (p60) and 43 (p43) kDa, prominent among crosslinking bands, were competed for by unlabeled substrate, but not by nonspecific RNA, and did not crosslink to antisense RNA. Editing in vitro and UV crosslinking were inhibited by NaCl and vanadyl ribonucleoside complexes and by chemical modification of sulfhydryl, imidazolium, and guanidinium groups on the protein. The editing activity copurified predominantly with p60. To define the binding site for p60 on the substrate RNA, a series of scanning and point mutant RNAs, previously used to define nucleotides 6671-6681 as essential for editing, were used in competition studies with wild-type substrate. Results demonstrated that p60 binding is centered on nucleotides 6671-6674. We suggest that p60 contains the RNA-recognition component of the apoB mRNA-editing enzyme.

Animals↗
PubMed1993

Characterization of genetic markers in the 5'flanking region of the apo A1 gene.

Genetic variation of apo A1/C3/A4 is associated with hyperlipidaemia and coronary heart disease. We report the polymerase chain reaction (PCR) conditions for determining three polymorphic sites in the 5'flanking region of apoA1 using DNA prepared from small aliquots of whole blood. These polymorphisms identify six haplotypes that will be of value in genetic studies.

Apolipoprotein A-I↗
PubMed1993

Olfactory dysfunction in the Shy-Drager syndrome.

The aetiology of the Shy-Drager syndrome (multiple system atrophy) is unknown. We reported previously a preliminary association between environmental-occupational risk factors and Shy-Drager syndrome. To further investigate this relationship, we evaluated olfactory function in eight patients in different stages of disease. When the eight patients' olfactory function was compared with 203 age- and sex-matched controls using a self-administered olfactory test, seven scored below the 39th percentile of this population. Five of the eight patients had total anosmia or microsmia. Additional studies will be required to elucidate the significance of this abnormal clinical observation.

Aged↗
PubMed1993

External ear resonance as a screening technique in children with otitis media with effusion.

External ear resonance can be quickly and accurately measured using real ear insertion gain equipment. It has been previously shown that external ear resonance characteristics are often altered by the presence of middle ear fluid. The external ear resonance characteristics of 84 children with a history of chronic middle ear disorder were determined. Results were compared to other audiological data and otological findings recorded during surgery. External ear resonance peak amplitude was significantly correlated with the presence or absence of middle ear fluid. It was found that peak amplitude of > or = 24 dB was associated with only 15% of dry ears and peak amplitude of < or = 22 dB associated with 79% of ears without fluid. The use of external ear resonance measures as a potential screening procedure is discussed.

Acoustic Impedance Tests↗
PubMed1993

A phase II evaluation of human lymphoblastoid interferon (Wellferon) in relapsed high grade malignant glioma. Medical Research Council Brain Tumour Working Party.

During the 1980s a number of studies suggested there might be a role for interferon in the treatment of high grade gliomas. In the light of these reports a formal Phase II evaluation of human lymphoblastoid interferon (Wellferon) was undertaken in patients with high grade gliomas which had relapsed after conventional radiotherapy; 14 patients were treated and no objective clinical responses were seen. This indicates that the overall response rate to interferon therapy in this situation would be less than 20%. It is therefore concluded that interferon administration is unlikely to be of value in the management of relapsed high grade gliomas.

Adult↗
PubMed1993

Oral piritrexim, an effective treatment for metastatic urothelial cancer.

Piritrexim is a lipid-soluble inhibitor of dihydrofolate reductase (DHFR) that enters tumour cells rapidly by passive diffusion, cannot be polyglutamated, and is as effective as methotrexate in inhibiting DHFR. Bioavailability after oral dosing is approximately 75%. We performed a phase II study with oral piritrexim in non-chemotherapy pretreated patients with metastatic urothelial cancer. Thirty-three patients were treated with 25 mg three times daily for 5 consecutive days, repeated weekly, with provision for dose escalation or reduction according to the toxicity observed. Of 29 evaluable patients, one patient achieved a complete response of 19+ weeks duration, and ten patients achieved a partial response with a median duration of 22 weeks (range 16-48), for a total response rate of 38%. Piritrexim was generally well tolerated, with myelosuppression as the major toxicity, that frequently required dose modification. We conclude that piritrexim appears to be an active agent in patients with metastatic urothelial cancer when administered as a 5-day, low-dose oral schedule. It would be attractive to investigate the combination of piritrexim and cisplatin.

Administration, Oral↗