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Biomedical subjects

S Joseph

Publications and source records attributed to S Joseph.

222 records · Page 13Linked to original sources
PubMedDate not supplied

Structure and function of ribosomal RNA.

A refined model has been developed for the folding of 16S rRNA in the 30S subunit, based on additional constraints obtained from new experimental approaches. One set of constraints comes from hydroxyl radical footprinting of each of the individual 30S ribosomal proteins, using free Fe(2+)-EDTA complex. A second approach uses localized hydroxyl radical cleavage from a single Fe2+ tethered to unique positions on the surface of single proteins in the 30S subunit. This has been carried out for one position on the surface of protein S4, two on S17, and three on S5. Nucleotides in 16S rRNA that are essential for P-site tRNA binding were identified by a modification interference strategy. Ribosomal subunits were partially inactivated by chemical modification at a low level. Active, partially modified subunits were separated from inactive ones by binding 3'-biotinderivatized tRNA to the 30S subunits and captured with streptavidin beads. Essential bases are those that are unmodified in the active population but modified in the total population. The four essential bases, G926, 2mG966, G1338, and G1401 are a subset of those that are protected from modification by P-site tRNA. They are all located in the cleft of our 30S subunit model. The rRNA neighborhood of the acceptor end of tRNA was probed by hydroxyl radical probing from Fe2+ tethered to the 5' end of tRNA via an EDTA linker. Cleavage was detected in domains IV, V, and VI of 23S rRNA, but not in 5S or 16S rRNA. The sites were all found to be near bases that were protected from modification by the CCA end of tRNA in earlier experiments, except for a set of E-site cleavages in domain IV and a set of A-site cleavages in the alpha-sarcin loop of domain VI. In vitro genetics was used to demonstrate a base-pairing interaction between tRNA and 23S rRNA. Mutations were introduced at positions C74 and C75 of tRNA and positions 2252 and 2253 of 23S rRNA. Interaction of the CCA end of tRNA with mutant ribosomes was tested using chemical probing in conjunction with allele-specific primer extension. The interaction occurred only when there was a Watson-Crick pairing relationship between positions 74 of tRNA and 2252 of 23S rRNA. Using a novel chimeric in vitro reconstitution method, it was shown that the peptidyl transferase reaction depends on this same Watson-Crick base pair.

Models, Biological↗
PubMedDate not supplied

Screening 1140 fifth graders for hypercholesterolemia: family history inadequate to predict results.

Cholesterol screening was performed on 1140 fifth-grade students in Scottsdale, AZ, as part of a school-affiliated, health-education program. The goals were to determine whether family history of heart disease or high cholesterol can predict which children have high cholesterol levels and to examine the feasibility of screening large numbers of elementary school students. Among the children studied, the mean cholesterol level was 168.3 mg/dL (4.35 mmol/L), and 13 percent had cholesterol levels above 200 mg/dL (5.20 mmol/L). Fifty-four percent had a family member with high cholesterol or a heart attack before age 60 years, but 36 percent of the students with cholesterol levels greater than 200 mg/dL (5.20 mmol/L) had a negative family history. Family history was neither sensitive nor specific as a predictor of elevated cholesterol levels (sensitivity 0.64, specificity 0.47, and positive predictive value 0.16 for predicting cholesterol levels greater than 200 mg/dL [5.20 mmol/L]). Large numbers of children were screened safely and efficiently with good student and parental cooperation. Results of this study do not support the current recommendations to screen children for hypercholesterolemia based upon their family histories.

Adolescent↗
PubMedDate not supplied

Dissolution of isobutyl 2-cyanoacrylate on long-term follow-up.

Eight patients with arteriovenous malformations (AVMs) in the basal ganglionic and deep parietooccipital regions and one patient with an AVM in the shoulder region showed resorption of the isobutyl 2-cyanoacrylate cast and recanalization of the arteries after delayed follow-up angiography. All the AVMs were large, had multiple arterial pedicles, and revealed significant obliteration of the AVM immediately after embolotherapy. Although a 50-75% obliteration was achieved immediately after embolization, follow-up angiography 6-20 months later revealed almost the original status. The residual bucrylate cast was disproportionately small compared with the recanalized malformation in seven patients, while in two patients there was no evidence of bucrylate on plain films. Degradation of bucrylate probably is due to the lysosomal activity of the endothelial cells. The results from our nine patients with some degree of resorption of isobutyl 2-cyanoacrylate and six with recanalized AVMs 6-20 months after embolization suggest that operable AVMs should be excised soon after embolotherapy and inoperable AVMs should be embolized as completely as possible.

Absorption↗
PubMedDate not supplied

Balloon angioplasty of the femoro-popliteal segment: follow up results from southern India.

BACKGROUND: Disease of the femoral and popliteal arteries, though one of the commonest manifestations of atherosclerosis, is under-recognized because the morbidity it produces is less catastrophic than coronary or cerebrovascular arterial involvement. Percutaneous transluminal angioplasty is performed for femoro-popliteal lesions at different centres in India, but post-angioplasty follow up data are scarce. We present our results after femoro-popliteal balloon angioplasty in 140 lesions. METHODS: Between 1986 and 1993, 140 femoro-popliteal angioplasties were performed in 119 patients with symptomatic limb ischaemia. Seventy-one per cent of patients had claudication and the others also had tissue loss. Eighty-two per cent of the lesions were occlusions. The average length of the lesions was 10.7 cm. Conventional wire-balloon angioplasty was performed in 128 lesions; in 12 others, laser-assisted balloon angioplasty was performed using an Nd-YAG laser thermal probe. Patients were followed up at regular intervals for any recurrence of symptoms and for objective evidence of restenosis or re-occlusion. RESULTS: Despite a technical success in 83% of the lesions, cumulative primary patency calculated by the life-table method showed a slow decline which plateaued at 40% after 36 months. Long occlusions and multifocal stenoses showed shorter cumulative patency following angioplasty (27 months and 5.8 months respectively). Extensive luminal irregularity due to post-angioplasty intimal flaps was reduced by using warm contrast for balloon dilatation in 16 patients. In 14 patients who had repeat angioplasty for restenosis, the secondary patency showed a satisfactory figure of 84% at 60 months. CONCLUSION: Percutaneous transluminal angioplasty is a satisfactory alternative to surgery in femoro-popliteal stenotic or occlusive disease. Regular follow up of such patients is essential in the first three years because re-occlusion can occur. We found that patency remained fairly constant after 36 months. Repeated angioplasty can maintain patency in patients with restenosis.

Adult↗