PubMed Health⌕ Search

Biomedical subjects

S Snape

Publications and source records attributed to S Snape.

13 recordsLinked to original sources
PubMed2005

A randomized controlled trial of botulinum toxin on lower limb spasticity following acute acquired severe brain injury.

OBJECTIVE: To determine whether serial casting combined with botulinum toxin reduces the development of calf contracture after severe head injury. DESIGN: A double-blind placebo-controlled trial of three parallel treatments for lower limb spasticity. SETTING: Acute general hospital in the UK. SUBJECTS: Adults aged 17-70 years admitted to hospital following a severe brain INTERVENTIONS: Current physical treatment (group I), lower leg casting plus injections with either saline (group II), or with botulinum toxin (group III) into gastrocnemius and soleus muscles. MEASURES: Limit of ankle dorsiflexion at entry and exit after up to 12 weeks, the Glasgow Outcome Scale (GOS) and Modified Ashworth Scale (MAS). RESULTS: Two hundred and fifty-three patients were screened and 35 were entered into the trial. Three patients died and four failed to complete the trial. Eighty-eight per cent of those entering the randomized part of the study developed spasticity within 14 days of their injury and the mean range of improvement in the angle of passive ankle dorsiflexion was 4.59 degrees in controls, 11.69 degrees in cast and saline and 13.59 degrees in cast and botulinum toxin. There were significant improvements in the MAS scores in actively treated groups, but not in controls. Cast and botulinum toxin patients also demonstrated a significant improvement in the GOS. CONCLUSIONS: Active intervention with casting prevents talipes equinovarus deformities in patients losing ankle movement following severe brain injury. Casting alone in these patients is sufficient; the role of additional botulinum toxin needs further investigation, but is safe in these patients.

Adolescent↗
PubMed1998

Endogenous interleukin-10 modulates proinflammatory response in Plasmodium falciparum malaria.

Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 are implicated in the pathogenesis of severe Plasmodium falciparum malaria. In this study, the effect of IL-10 on their production by peripheral blood mononuclear cells (PBMC) from acutely infected patients was examined. Exogenous IL-10 inhibited malarial antigen-induced cytokine production by reducing mRNA accumulation. Maximal inhibition occurred when IL-10 was added in the first 2 h of stimulation. Conversely, the addition of anti-IL-10 markedly enhanced TNF-alpha, IL-1beta, and IL-6 production. The effect was significantly greater on PBMC from patients with uncomplicated infection than PBMC from patients with severe disease. Kinetics studies showed that TNF-alpha, IL-6, and IL-1beta were produced within 2-4 h of stimulation, while IL-10 was first detectable after 8 h. These findings suggest that IL-10 counter-regulates the proinflammatory response to P. falciparum. Severe falciparum malaria may be associated with an inadequate negative feedback response by IL-10.

Adult↗
PubMed1998

Functional characterization of alternatively spliced human SERCA3 transcripts.

The sarcoplasmic (or endoplasmic) reticulum Ca2+-ATPase (SERCA)-3 has been implicated in the possible dysregulation of Ca2+ homeostasis that accompanies the pathology of hypertension and diabetes. We report the molecular cloning of two alternatively spliced transcripts from the human SERCA3 gene, ATP2A3, that encode proteins that differ at their carboxy termini by 36 amino acids. SERCA3 transcripts were most abundantly expressed in lymphoid tissues, intestine, pancreas, and prostate. The two human SERCA3 proteins encoded by alternatively spliced transcripts were recognized by the monoclonal antibody PL/IM430 and demonstrated Ca2+ uptake and ATPase activity with an apparent Ca2+ affinity 0.5 pCa unit lower than that of other SERCA gene products. The subcellular distribution of SERCA3 protein was indistinguishable from that of SERCA2b, with expression in the nuclear envelope and in the endoplasmic reticulum throughout the cell. Two variant SERCA3 constructs, huS3-I and huS3-II, were isolated that encode proteins with three amino acid differences: Ala-673 (in huS3-I) substituted for Thr (in huS3-II), Ile-817 substituted for Met, and an insertion of Glu-994. huS3-I displayed a 10-fold lower capacity to transport Ca2+ than huS3-II.

Alternative Splicing↗
PubMed1991

Iron binding to, and release from, the basolateral membrane of mouse duodenal enterocytes.

The basolateral membrane of mouse duodenal enterocytes can be selectively labelled in vitro with 59Fe by incubating intact enterocytes with 59Fe(III)-nitrilotriacetate at 0-4 degrees C. It has been proposed that this labelling represents binding to a site important in the transfer of intracellular Fe to the portal plasma (Snape, S., Simpson, R.J. and Peters, T.J. (1990) Cell Biochem. Funct. 8, 107-115). Studies presented here show binding to intact enterocytes in vitro was complete within 1 h and was proportional to enterocyte protein concentration. Binding to enterocytes isolated from both normal and chronically hypoxic mice showed a hyperbolic dependence on medium Fe(III) concentration, consistent with a single class of binding sites. Neither apparent binding constant nor maximal binding were increased by hypoxic exposure of mice, suggesting that the increased in vivo labelling of this site in hypoxia is not due to an increase in affinity or capacity of this site for iron. Release of iron from intact enterocytes, labelled at 0-4 degrees C, was measured at 37 degrees C and 0-4 degrees C. Release of 59Fe was extensive and more rapid at 37 degrees C with highest release to mouse serum. Iron released to serum was found to be bound to transferrin. Prior dialysis of serum against buffer led to complete failure of enterocytes to release iron. Reconstituting serum by adding back the dialysate restores release to levels seen in fresh serum, suggesting that low molecular weight serum components, notably bicarbonate, mediate iron transfer from the basolateral membrane to serum transferrin. The properties of the basolateral membrane iron binding site described here are consistent with a role in the iron transfer process.

Animals↗
PubMed1990

Subcellular localization of recently-absorbed iron in mouse duodenal enterocytes: identification of a basolateral membrane iron-binding site.

The subcellular distribution of newly absorbed iron in isolated mouse duodenal enterocytes was investigated by analytical subcellular fractionation using sucrose density gradient centifugation. Two major peaks of mucosal 59Fe activity were observed: one soluble and one particulate (density 1.18-1.20 g ml-1). The latter was increased following prior exposure of animals to chronic hypoxia. The particulate 59Fe was localized to the basolateral membranes using the marker enzyme Na+, K+ activated, Mg2+ dependent, ATPase and by washing intact enterocytes with the selective plasma membrane perturbant digitonin. The basolateral membrane can be selectively labelled by in vitro incubation of intact enterocytes at 0 degrees C with 59Fe(III)-nitrilotriacetate complex, confirming the presence of a 59Fe binding site on this membrane. No significant difference in in vitro iron binding to this site was observed between normal and chronically hypoxic animals. Iron binding to the basolateral membrane was significantly higher in disrupted, compared to intact enterocytes, indicating that this site is present on both sides of the basolateral membrane. It is therefore suggested that the increased labelling of this site in hypoxia, in vivo, is a consequence of an increase in a mucosal Fe pool which is available for binding to a membrane receptor.

Adenosine Triphosphatases↗
PubMed1988

Subcellular distribution of recently absorbed iron and of transferrin in the mouse duodenal mucosa.

A successful method for the analytical subcellular fractionation of mouse duodenal mucosa organelles was established. 59Fe(III)-nitrilotriacetate (pH 7.2) was injected into tied-off duodenal segments in vivo and, after 2-20 min, mucosal homogenates were subjected to subcellular fractionation. Radioactivity was recovered in the cytosolic fractions and in the gradient at a density of 1.18-1.20 g/ml. Enhanced iron absorption was achieved by placing the animals in a hypobaric chamber for 3 days. These animals had a higher proportion of particulate 59Fe compared to controls. Homogenisation in sucrose medium containing the selective plasma membrane perturbant digitonin shifted the particulate iron fraction to a higher density region of the gradient indicating a localisation of the iron binding site to the plasma membrane region of the mucosal cells. No significant radioactive iron was observed in the brush-border region of the gradient. Transferrin immunoreactivity was found only in the cytosolic region of the gradient and was not associated with any organelle.

Animals↗
PubMed1987

Intestinal iron absorption and mucosal transferrin in rats subjected to hypoxia.

Three days hypoxia (0.5 atm) increased the haemoglobin and haematocrit values in rats paralleled by enhanced intestinal iron absorption. The destination of recently-absorbed iron was primarily the erythropoietic system, viz. bone marrow, spleen and red cells. Total plasma transferrin, was increased by 30%, but no significant changes in mucosal transferrin were found. No increase in labelling of mucosal transferrin by absorbed iron was observed. These results suggest that mucosal transferrin does not play a major role in the regulation of intestinal iron absorption in hypoxia.

Animals↗
PubMed1986

Galactosyltransferase activity is not localized to the brush border membrane of human small intestine.

A recent report [Roth et al. (1985) J. Cell Biol. 100: 118-125], using immunocytochemical techniques, claimed that human duodenal galactosyltransferase is located predominantly on the external aspect of enterocyte brush border membranes. Analytical subcellular fractionation by sucrose density gradient centrifugation of human jejunum biopsy homogenates demonstrated that galactosyltransferase activity is localized to the Golgi fraction (equilibrium density of 1.14 g cm-3) and is not found in significant amounts in the brush border membrane (equilibrium density of 1.22 g cm-3).

Centrifugation, Density Gradient↗
PubMed1978

A survey of the haematological, nutritional and biochemical state of the rural elderly with particular reference to vitamin C.

A survey of the rural elderly has been carried out to determine basic haematological and biochemical data, and to establish a pattern of living for this 'well' population. The blood parameters related to diet, such as haemoglobin, folate, cholesterol, vitamin C etc., show considerable changes with increasing age in the male but little significant change in the female. The vitamin C status for both sexes compares favourably with that reported by other workers studying the urban elderly. The biochemical and haematological data derived provide a normal range with which the 'sick' elderly can be compared. The subjects were generally active and independent in spite of (or because of) a somewhat Spartan existence.

Adolescent↗