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Biomedical subjects

S Joseph

Publications and source records attributed to S Joseph.

At least 109 records · Page 6Linked to original sources

Low prevalence of human T lymphotropic virus type I in !Kung San in Bushmanland, Namibia.

Antibodies to human immunodeficiency virus 1 (HIV-1) and human T lymphotropic virus type 1 (HTLV-I) have been identified in various population groups living in southern and central Africa. Sera from 291 !Kung Bushmen in Bushmanland, Namibia were examined for the presence of antibodies to HIV-1 and HIV-2 and to HTLV-I. Initial screening for HIV-1/2 by two enzyme-linked immunosorbent assays (ELISAs) revealed evidence of past exposure in four individuals. However, no HIV-1/2 infection could be confirmed by a particle agglutination assay, a recombinant ELISA, or by Western blot for HIV-1 and HIV-2. Indeterminate Western blot profiles (with a p55 for each and either a p25 or p18 band) existed for all four HIV-1-reactive sera. Eight sera were reactive in the HTLV-I ELISA, although only five were positive on a second ELISA. Only three of the five HTLV-I-reactive sera could be confirmed by Western blot.

Adolescent↗

Focal occlusive disease of the common femoral artery: a report of 20 cases.

Occlusive disease localized to the common femoral artery without contiguous involvement of the external iliac and superficial femoral arteries is distinctly uncommon in vascular surgical practice. Twenty patients with focal occlusive disease in 21 common femoral arteries are featured in this report. All except one had severe disabling symptoms: Fontaine classification was stage I in one patient, stage IIb in 13, and stage III in six patients. The probable aetiology, based on clinical features and angiographic observations, was identified as atherosclerosis (nine cases), thromboangiitis obliterans (three) and Takayasu's arteritis (two). Histological features of mucoid vasculopathy, a novel disorder, was seen in one patient while no specific aetiology was evident in five patients. Associated lesions were seen in fourteen patients: aortoiliac in one, femoropopliteal in seven (without any continuity to the common femoral lesion), internal iliac in three and tibial in three. Balloon angioplasty of the common femoral artery lesions was attempted in 14 patients with successful outcome in nine. Three patients (including two with failed balloon angioplasty), underwent thromboendarterectomy and two bypass procedures (iliofemoral, one; femoropopliteal, one). Late reocclusion occurred in one patient each in the angioplasty and surgical groups. There were no procedure-related complications in either group.

Adolescent↗

Angiographic analysis and results of endovascular therapy of aneurysm of vein of Galen.

Angioarchitecture of the aneurysmal malformation of the vein of Galen in 9 patients is analysed. An arterial maze arborised directly into the vein of Galen in 6 patients. Direct fistulous communication from one or two pedicles was noted in three children. Unilateral choroidal arterial contribution via an eccentric cul-de-sac in two infants suggested embryonic involvement of the ipsilateral internal cerebral vein along with the median prosencephalic vein of Markowski. Unusually, a sylvian branch of the middle cerebral artery drained directly into the basal vein of Rosenthal which in turn communicated to the aneurysm of vein of Galen in another patient. Two adult patients had curvilinear rim calcification of the venous sac with rapid circulation. All but two showed venous sinus anomalies. Two children had prior shunt surgery at the referring hospitals. The pathophysiology of hydrocephalus and the possible consequences of shunt, question the need for CSF diversion as a routine in these patients. Percutaneous trans-arterial embolotherapy, in five patients achieved complete obliteration of the malformation in four patients and partial reduction of flow in another. While transvenous/trans-torcular approach is reserved for selected patients and direct surgery carries high morbidity, this report emphasises the efficacy of trans-arterial embolotherapy.

Adult↗

Optimization of an anti-HIV hairpin ribozyme by in vitro selection.

We have applied in vitro selection methods to achieve a large increase in the catalytic activity of a hairpin ribozyme targeted against a highly conserved 14-nucleotide sequence within HIV-1 pol RNA. The substrate specificity was changed by mutating 8 bases within the substrate-binding domain of the parental (-)sTRSV ribozyme. The resulting enzyme cleaved the HIV substrate specifically but with a 20-fold reduction in catalytic efficiency (kcat/KM). Following random mutagenesis, ribozymes with increased activity against the target sequence were selected through 10 rounds of in vitro selection. Selective pressure was increased by decreasing MgCl2 and spermidine concentrations, and reducing reaction time. Variant ribozymes with base substitutions A11-->G and U39-->C were selected in the population. These mutations were introduced singly and in combination into the trans-acting anti-HIV ribozyme. Each of the single-base substitutions significantly increased ribozyme activity, while the activity of double mutant was increased to nearly the level of the parental ribozyme. These findings demonstrate that in vitro selection is a powerful and efficient method to optimize ribozymes for the catalytic inactivation of targeted RNA molecules.

Base Sequence↗

The N-terminal thrombin receptor fragment SFLLRN, but not catalytically inactive thrombin-derived agonists, activate U937 human monocytic cells: evidence for receptor hydrolysis in thrombin-dependent signalling.

It has previously been reported that murine macrophages can respond chemotactically and mitogenically to the serine proteinase thrombin. There is a similar response in these macrophages to catalytically inactivated thrombin or to peptide fragments of the thrombin B-chain [Bar-Shavit, Kahn, Mann and Wilner (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 976-980]. However, the existence of a non-proteolytic mechanism of thrombin receptor activation in mononuclear cells was not evident in the present study using U937 human monocytic cells. The ability of thrombin to stimulate intracellular Ca2+ mobilization, actin polymerization or cell proliferation was not mimicked by N alpha-tosyl-L-lysine chloromethyl ketone (TLCK)-treated thrombin or by a synthetic 14-amino-acid peptide (single amino acid letter code YPPWNKNFTENDLL) corresponding to a part of the B-chain of thrombin which was reported to be mitogenic in murine macrophages. Evidence was obtained, however, in U937 cells for the presence of proteolytic-dependent thrombin receptor similar to the thrombin receptor expressed in platelets, which following thrombin cleavage exposes a new N-terminal tethered ligand. In support of this, a thrombin-receptor-derived hexapeptide (TRP; sequence SFLLRN), corresponding to a part of the thrombin receptor tethered ligand, mimicked all the actions of thrombin in U937 cells. Further, TRP and thrombin cross-desensitized U937 cells to subsequent stimulation with either TRP or thrombin, suggesting that TRP acted through the same U937 cell surface receptor as did thrombin. Thrombin activation of U937 monocytic cells can therefore be accounted for entirely by a proteolytic mechanism of thrombin receptor activation.

Actins↗

Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme.

In vitro selection experiments have been used to isolate active variants of the 50 nt hairpin catalytic RNA motif following randomization of individual ribozyme domains and intensive mutagenesis of the ribozyme-substrate complex. Active and inactive variants were characterized by sequencing, analysis of RNA cleavage activity in cis and in trans, and by substrate binding studies. Results precisely define base-pairing requirements for ribozyme helices 3 and 4, and identify eight essential nucleotides (G8, A9, A10, G21, A22, A23, A24 and C25) within the catalytic core of the ribozyme. Activity and substrate binding assays show that point mutations at these eight sites eliminate cleavage activity but do not significantly decrease substrate binding, demonstrating that these bases contribute to catalytic function. The mutation U39C has been isolated from different selection experiments as a second-site suppressor of the down mutants G21U and A43G. Assays of the U39C mutation in the wild-type ribozyme and in a variety of mutant backgrounds show that this variant is a general up mutation. Results from selection experiments involving populations totaling more than 10(10) variants are summarized, and consensus sequences including 16 essential nucleotides and a secondary structure model of four short helices, encompassing 18 bp for the ribozyme-substrate complex are derived.

Base Sequence↗

Arteriovenous aneurysm of the occipital artery.

We report an unique case of a giant aneurysm of the occipital artery, with a venous connection to the transverse sinus via an emissary vein. Because of this connection, the term arteriovenous aneurysm is used.

Catheterization↗

Aortoarteritis of abdominal aorta: an angiographic profile in 110 patients.

The angiographic appearances in 110 patients (49 males, 61 females, age range 11-46 years, mean 27.8 years) with aortoarteritis involving the abdominal aorta and/or its branches were analysed. There were 41 aneurysms of the abdominal aorta in 37 patients and eight aneurysms of its branches in as many patients. In 50 patients, 53 obstructive lesions involved the abdominal aorta and were classified as stenoses of focal, segmental and diffuse types and total occlusions. Branch obstructions (182 lesions in 85 patients) affected in order of frequency, the renal, superior mesenteric, coeliac, iliac and the inferior mesenteric arteries. Mesenteric arterial lesions were significantly more common in males (P = 0.01). Collateral circulation through a prominent mesenteric arcade was a distinctive angiographic feature in 28 patients. Computed tomography done in four patients showed peri-adventitial thickening and layered thrombus within aneurysms in three patients, and luminal occlusion of the upper abdominal aorta in one patient. Angiographic appearances in aortoarteritis of the abdominal aorta are characteristic and sufficiently distinctive for definitive diagnosis and appropriate management.

Adolescent↗

Multiple pulmonary-artery aneurysms due to mucoid vasculopathy--angiographic and histological observations.

Multiple peripheral pulmonary artery aneurysms were diagnosed by computed tomography and confirmed angiographically in a 7-year-old boy. On histological examination unusual mucoid vasculopathic changes were noted in the pulmonary artery aneurysms and pulmonary vasculature as a part of systemic vascular involvement. This case demonstrates a new association between mucoid vasculopathic changes and pulmonary aneurysms. Mucoid vasculopathy could represent one more disorder having a causative role in the etiology of intrapulmonary arterial aneurysms.

Aneurysm↗

Self-perception profile of adolescent girls at a single-sex and a mixed-sex school.

The aim of this study was to investigate the association between attendance at either a single- or a mixed-sex school and scores on the Self-Perception Profile for Children (Harter, 1985). Subjects included 143 Northern Irish adolescent girls from a single-sex secondary school in Belfast and 24 adolescent girls from a mixed-sex secondary school matched for location and religious affiliation. Results indicated that girls from the single-sex school were less happy than girls at the mixed-sex school with respect to their physical appearance, but more satisfied with their behavioral conduct. In addition, physical appearance was the best predictor of global self-worth for girls at the mixed-sex school, whereas behavioral conduct was the best predictor of global self-worth for girls at the single-sex school.

Adolescent↗

Substrate selection rules for the hairpin ribozyme determined by in vitro selection, mutation, and analysis of mismatched substrates.

Substrate recognition by the hairpin ribozyme has been proposed to involve two short intermolecular helices, termed helix 1 and helix 2. We have used a combination of three methods (cleavage of mismatched substrates, in vitro selection, and site-specific mutational analysis) to systematically determine the substrate recognition rules for this RNA enzyme. Assays measuring substrate cleavage in trans under multiple turnover conditions were conducted using the wild-type ribozyme and substrates containing mismatches in all sites potentially recognized by the ribozyme. Molecules containing single- and multiple-base mismatches in helix 2 at sites distant from the cleavage site (g-4c, u-5a, g-4c: u-5a) were cleaved with reduced efficiency, whereas those with mismatches proximal to the cleavage site (c-2a, a-3c, c-2a: a-3c) were not cut. Analogous results were obtained for helix 1, where mismatches distal from the cleavage site (u+7a, u+8a, u+9a, u+7a: u+8a: u+9a) were used much more efficiently than those proximal to the cleavage site (c+4a, u-5a, g+6c, c+4a: u+5a: g+6c). In vitro selection experiments were carried out to identify active variants from populations of molecules in which either helix 1 or helix 2 was randomized. Results constitute an artificial phylogenetic data base that proves base-pairing of nucleotides at five positions within helix 1 and three positions within helix 2 and reveals a significant sequence bias at 3 bp (c+4.G6, c-2.G11, and a-3.U12). This sequence bias was confirmed at two sites by measuring relative cleavage rates of all 16 possible dinucleotide combinations at base pairs c+4.G6 and c-2.G11.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Crisis support in the aftermath of disaster: a longitudinal perspective.

Crisis support was assessed over an 18-month period with survivors of the Jupiter cruise ship disaster. It was found that the support received from family and friends decreased significantly over time. In addition, higher crisis support in the immediate aftermath was found to predict less post-traumatic symptomatology at a later period. The results are thought to have implications for the assessment and treatment of survivors at high risk of disturbance.

Adaptation, Psychological↗

Increased substance use in survivors of the Herald of Free Enterprise disaster.

Cross-sectional data are reported on 73 survivors of the Herald of Free Enterprise disaster. Many reported an increase in their consumption of alcohol, cigarettes, sleeping tablets, antidepressants and tranquillizers at six and 30 months. The level of increased use was, however, lower at 30 months than at six months, although this was less evident for alcohol and cigarettes than the other substances. In addition, self-reports of increased substance use are associated with higher levels of psychological distress as measured by the General Health Questionnaire and the Impact of Events Scale. It is suggested that substance use might help to maintain subsequent psychological distress.

Adolescent↗

Takayasu arteritis: initial and long-term follow-up in 16 patients after percutaneous transluminal angioplasty of the descending thoracic and abdominal aorta.

PURPOSE: To analyze results of percutaneous transluminal angioplasty (PTA) for stenosis of the descending thoracic and/or abdominal aorta caused by Takayasu arteritis (TA). MATERIALS AND METHODS: Subjects were 16 patients (12 female and four male, aged 6-46 years) with symptoms of hypertension or severe bilateral lower limb claudication. Total aortography revealed stenotic lesions in the descending thoracic aorta in five, in the abdominal aorta in 10, and in both vessels in one patient. Involvement of arch vessels in four patients and of the renal artery in four patients was also noted. Double-balloon angioplasty was performed in eight patients. RESULTS: Initial technical and clinical success was 100%. The maximum follow-up period was 52 months (mean, 21 months 2 weeks). Ankle-brachial index as determined with Doppler ultrasound improved considerably in 10 patients. Three patients had symptoms of restenosis during follow-up. Cumulative patency rate by life-table analysis was 67%. CONCLUSION: PTA has a definite role in the management of TA in view of its procedural simplicity, cost-effectiveness, and results compared with surgical revascularization procedures.

Adolescent↗