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Biomedical subjects

A Newman

Publications and source records attributed to A Newman.

At least 73 records · Page 4Linked to original sources
PubMed1992

Outcome of coronary artery aneurysms after Kawasaki disease.

From 1974 through 1991, a total of 583 children with Kawasaki disease were seen at the Hospital for Sick Children, in Toronto, of whom 80 (13.7%) had coronary artery involvement. There were 55 boys and 25 girls, whose mean age at onset was 2.9 +/- 2.5 years, followed for a mean period of 4.0 +/- 3.6 years. Giant aneurysms (maximum diameter > or = 8 mm) were found in 22 children, moderate-sized aneurysms (> or = 4 to < 8 mm) in 44, and dilation lesions (< 4 mm) in 14. Myocardial infarction occurred in 9 (1.5%), all of whom had giant aneurysms. The persistence rate for aneurysms was 72% at 1 year and 41% at 5 years of follow-up. In multivariate analysis, the regression of an aneurysm was significantly related to the severity of coronary artery lesions, initial treatment, and gender. Although > 80% of small or moderate-sized aneurysms regressed within 5 years, giant aneurysms did not regress during the follow-up period. In patients who received immune globulin therapy, coronary lesions tended to resolve more rapidly than in those treated with salicylate therapy alone, because 91% of the lesions in the former were small or moderate. These findings suggest that the severity of coronary artery involvement during the initial stages of Kawasaki disease influences the regression of these lesions, and that immune globulin treatment may improve outcome by reducing the incidence of severe lesions.

Adolescent↗
PubMed1991

Mutations in yeast U5 snRNA alter the specificity of 5' splice-site cleavage.

Recognition of 5' splice sites in pre-mRNA splicing is achieved in part by base pairing with U1 snRNA. We have used interactive suppression in the yeast Saccharomyces cerevisiae to look for other factors involved in 5' splice-site recognition. This approach identified an extragenic suppressor that activates a cryptic 5' splice site. The suppressor is a gene for U5 snRNA (snR7) with a single base mutation in a strictly conserved 9 base sequence. This suggests that U5 snRNA can play a part in determining the position of 5' splice-site cleavage. Consistent with this, we have been able to isolate other mutations in the 9 base element in U5 snRNA that specifically activate a second cryptic 5' splice site nearby.

Base Composition↗
PubMed1991

The Cardiovascular Health Study: design and rationale.

The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of coronary heart disease and stroke in adults aged 65 years and older. The main objective of the study is to identify factors related to the onset and course of coronary heart disease and stroke. CHS is designed to determine the importance of conventional cardiovascular disease (CVD) risk factors in older adults, and to identify new risk factors in this age group, especially those that may be protective and modifiable. The study design called for enrollment of 1250 men and women in each of four communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. Eligible participants were sampled from Medicare eligibility lists in each area. Extensive physical and laboratory evaluations were performed at baseline to identify the presence and severity of CVD risk factors such as hypertension, hypercholesterolemia and glucose intolerance; subclinical disease such as carotid artery atherosclerosis, left ventricular enlargement, and transient ischemia; and clinically overt CVD. These examinations in CHS permit evaluation of CVD risk factors in older adults, particularly in groups previously under-represented in epidemiologic studies, such as women and the very old. The first of two examination cycles began in June 1989. A second comprehensive examination will be repeated three years later. Periodic interim contacts are scheduled to ascertain and verify the incidence of CVD events, the frequency of recurrent events, and the sequellae of CVD.

Aged↗
PubMed1991

Grading written essays: a reliability study.

The purpose of this study was to examine the interrater reliability of grades obtained by physical therapy and occupational therapy tutors in rating their students' term papers. This study was carried out in two phases. In phase 1, four student essay papers (two physical therapy students' papers and two occupational therapy students' papers) with grades that had been assigned from the previous year's course were randomly selected from a bank of papers. These papers were independently rated by three course planners (who were responsible for planning, coordinating, and tutoring in the course), and agreement as to the assignment of grades for each paper was established. In phase 2, the same students' essays were rated independently by eight course tutors. To test for differences among students' written essay papers and for differences among the raters in the subcategories of discipline (physical therapy versus occupational therapy) and level of expertise (novice versus experienced) in grading essays, a three-way analysis of variance was performed. An intraclass correlation coefficient (ICC) was calculated for interrater reliability. Although there were no statistically significant differences among the tutors with regard to their discipline and expertise, the reliability analysis produced an ICC of .79. Strategies to enhance the reliability of grading essays are discussed.

Educational Measurement↗
PubMed1991

Midline nasal destruction in cocaine abusers.

Idiopathic midline destructive disease (IMDD) is a diagnosis of exclusion in patients who manifest midline nasal necrosis with no specific etiology such as infection, tumor, or Wegener's granulomatosis. Recently, a group of cocaine abusers has been identified that manifests a syndrome that mimics IMDD, but is less fulminant in its course. To better define the natural history of this syndrome, we reviewed the medical records, radiographs, and pathologic material from five such patients treated at the University of California, Los Angeles. Other causes of midline nasal destruction were excluded in each patient on the basis of histopathology, cultures, and laboratory tests. Biopsy material, available in four patients, demonstrated inflammation and necrosis without vasculitis. Treatment was conservative in four of the five patients, using antibiotics, local care, debridement, and cessation of cocaine use. During the follow-up period, progressive disease developed in one of the five patients, requiring radiation and steroid therapy. We conclude that the treatment of midline nasal destruction in cocaine abusers should initially be conservative, once other etiologies have been systematically excluded.

Adult↗
PubMed1990

The potent opioid agonist, (+)-cis-3-methylfentanyl binds pseudoirreversibly to the opioid receptor complex in vitro and in vivo: evidence for a novel mechanism of action.

The present study demonstrates that pretreatment of rat brain membranes with (+)-cis-3-methylfentanyl [(+)-cis-MF], followed by extensive washing of the membranes, produces a wash-resistant decrease in the binding of [3H]-[D-ala2,D-leu5]enkephalin to the d binding site of the opioid receptor complex (delta cx binding site). Intravenous administration of (+)-cis-MF (50 micrograms/kg) to rats produced a pronounced catalepsy and also produced a wash-resistant masking of delta cx and mu binding sites in membranes prepared 120 min post-injection. Administration of 1 mg/kg i.v. of the opioid antagonist, 6-desoxy-6 beta-fluoronaltrexone (cycloFOXY), 100 min after the injection of (+)-cis-MF (20 min prior to the preparation of membranes) completely reversed the catatonia and restored masked delta cx binding sites to control levels. This was not observed with (+)-cycloFOXY. The implications of these and other findings for the mechanism of action of (+)-cis-MF and models of the opioid receptors are discussed.

Animals↗
PubMed1989

Regulatory and essential light-chain-binding sites in myosin heavy chain subfragment-1 mapped by site-directed mutagenesis.

Site-directed mutagenesis of the cloned subfragment-1 (S-1) region of the unc-54 gene, encoding the myosin heavy chain B (MHC B) from Caenorhabditis elegans, has been used to locate binding sites for the regulatory and essential light chains. MHC B S-1 synthesized in Escherichia coli co-migrated with rabbit skeletal muscle myosin S-1 (Mr 90,000), was recognized by anti-nematode myosin antiserum on immunoblots, and specifically bound to 125I-labelled regulatory and essential light chains in a gel overlay assay. Deletion of 102 residues from the C terminus (mutant 655) reduced regulatory and essential light-chain binding to about 30% and 20% of wild-type levels, respectively. Similar reductions in relative binding of the two light chains were seen with mutant 534, in which 38 residues were deleted from the C terminus. Potential binding sites within 75 residues of the C terminus of S-1 were mapped by construction of five other mutant S-1 clones (398, 399, 400, 409 and 411) containing internal deletions of ten to 12 amino acid residues. These showed up to 30% reductions in their ability to bind essential light chains, but did not differ significantly from wild-type in their ability to bind regulatory light chains. Another mutant, 415, containing a deletion of a conserved acidic hexapeptide, E-D-I-R-D-E, showed enhancement of binding of regulatory and essential light chains to 150% and 165% of wild-type levels. Hence, the major binding sites for both light chains are within 38 amino acid residues of the C terminus.

Amino Acid Sequence↗
PubMed1989

Primary vestibular projections in the chinchilla.

The central projections of fibers from the vestibular nerve were studied in 19 chinchillas after horseradish peroxidase labelling. In addition, the limits of the vestibular nuclei and the anatomical characteristics of their neurons were also studied. All five vestibular nuclei received primary afferents, but there were extensive areas of them that received very little or no projections at all, such as the rostral part of the superior vestibular nucleus, the dorsocaudal part of the lateral vestibular nucleus, the caudal half of the medial vestibular nucleus and the caudalmost aspect of the dorsal vestibular nucleus.

Afferent Pathways↗
PubMed1989

Regeneration of the eighth cranial nerve. III. Central projections of the primary afferent fibers from individual vestibular receptors in the bullfrog.

The projection site in the central nervous system of individual end-organ branches of regenerated vestibular nerves was documented in bullfrogs. The eighth cranial nerve was surgically sectioned in 12 bullfrogs (Rana catesbeiana) and allowed to regenerate. Horseradish peroxidase was used to label the primary vestibular afferent fibers from the whole nerve (one frog) and the whole anterior branch (two frogs), and the individual receptor end-organ branches to the anterior semicircular canal (three frogs), the horizontal semicircular canal (three frogs), and the sacculus (three frogs). A sufficient number of fibers from the individual receptors were labeled in nine specimens to allow a description of their central projection pattern. The overall pattern of central projections of the regenerated nerves was similar to the pattern of normal nerves. In the eighth nerve root proper and in the area proximal to the vestibular nuclei, fibers from the anterior semicircular canal were ventral, fibers from the sacculus and posterior branch were dorsal, and fibers from the horizontal semicircular canal were in an intermediate position. In ventral, superior, and descending vestibular nuclei, a projection pattern was also identifiable in some specimens. The fibers of the anterior semicircular canal projected ventral to the fibers of the horizontal semicircular canal, with fibers from the posterior branch more dorsal. The saccular fibers projected to the dorsal aspect of the ventral nucleus and the ventral aspect of the dorsal nucleus. For the most part, projections in the regenerated specimens, as verified histologically, were comparable to individual end-organ projections previously identified in normal frogs. The only major discrepancy between the findings from the regenerated specimens and those from normal frogs was in the position of the vestibular tract and the innervation to the medial nucleus. The regenerated vestibular tract was shifted laterally in the brain stem. Regenerated thick and thin fibers were intermixed in the tract and projected to the medial nucleus. Normally, the thin fibers are lateral to the thick fibers in the tract. Therefore, the regenerated afferent fibers of the vestibular nerve selectively reinnervated the vestibular nuclei, and the fibers to the individual end-organs selectively reinnervated particular parts of the nuclei. In addition, the thick and thin regenerated fibers preserved the type of bouton endings normally found. The regenerated thick fibers had rare boutons en passant and a great number of collaterals, while the thin fibers had numerous boutons en passant and only a few collaterals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Specific accessory sequences in Saccharomyces cerevisiae introns control assembly of pre-mRNAs into spliceosomes.

In experiments involving deletion and rearrangement of intron sequences two small regions of the intron in the yeast CYH2 ribosomal protein gene were found to play important roles in splicing of the pre-mRNA. One element lies downstream of the 5' splice site, and the other is upstream of the branchpoint sequence UACUAAC. Deletion of the element upstream of the branchpoint prevents spliceosome formation and blocks splicing in vivo and in vitro. Deletion of the element downstream of the 5' splice site does not on its own block splicing but rescues spliceosome formation and splicing of pre-mRNA lacking the element upstream of the branchpoint. These elements correspond to two regions of sequence complementarity which are a conserved feature of the introns in yeast pre-mRNAs. Mixing and matching of the elements from the ACT1 and CYH2 gene introns showed that these elements can cooperate in an intron-specific fashion to control spliceosome assembly.

Base Sequence↗