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Biomedical subjects

S Martin

Publications and source records attributed to S Martin.

At least 91 records · Page 5Linked to original sources
PubMed2002

Effects of agent strain and host genotype on PrP accumulation in the brain of sheep naturally and experimentally affected with scrapie.

Different cellular and neuroanatomical types of disease-specific prion protein (PrP(d)) accumulation in the brain were identified in sheep of different breeds and PrP genotypes exposed to experimental or natural scrapie infection. Immunohistochemical examination of the brains of 43 sheep with clinical signs compatible with scrapie revealed 12 different PrP(d)types, which were subjectively quantified in eight different brain regions. The PrP(d)types were grouped into four PrP(d)patterns, the relative magnitude of which provided the PrP(d)profile of each sheep examined. The analysis of the differences in magnitude and relative proportion of each of these PrP(d)types and patterns indicated (1) an effect of the scrapie strain on the PrP(d)profile, and (2) a possible effect of the host genotype on the magnitude of PrP(d)accumulation in the brain, apparently related to the incubation period. Furthermore, intraneuronal deposition of PrP(d)was the type most closely associated with the development of clinical disease. We conclude that different scrapie strains can be distinguished by PrP immunohistochemical examination of brains of affected animals.

Animals↗
PubMed2002

Occurrence and distribution of infection-specific PrP in tissues of clinical scrapie cases and cull sheep from scrapie-affected farms in Shetland.

The prion protein (PrP) genotypes of all cull sheep originating from four scrapie-affected farms in Shetland in 1998-1999 were determined and a representative sample of the different genotypes was selected for necropsy. Samples of brain and selected viscera were removed from 159 such sheep aged 2-11 years. These samples were examined immunohistochemically and by Western blotting for infection-specific forms of PrP. None of the sheep bearing the following genotypes showed any evidence of PrP accumulation in brain, intestine, selected lymph nodes or the cranial mesenteric ganglia: ARQ/ARQ (n = 41), ARQ/ARH (n = 12), ARH/ARH (n = 2), ARQ/ARR (n = 24), ARR/ARR (n= 2). In five of 71 sheep bearing a single VRQ allele, PrP accumulation was detected immunohistochemically in viscera or brain, or both. These results suggested that only a small proportion of susceptible sheep showed evidence of infection (accumulation of PrP) on the farms studied, and that even sheep of the most susceptible genotype (VRQ/VRQ) did not invariably develop disease in an infected environment. Furthermore, there was no evidence that, in sheep of semi-resistant or fully resistant genotypes, infection could be sequestered within the lymphoreticular system or peripheral nervous system and thereby provide a possible "carrier" source of infection. Rather, the data suggested that some sheep, possibly because they had been exposed to a relatively low infective dose, became infected and accumulated the infective agent over a protracted pre-clinical phase of the disease. Such sheep might be potentially infective for many years. In two VRQ/ARR genotype sheep, PrP was confined to the brain. Infection-specific PrP was also confined to the brain in two of 24 clinical cases of VRQ/ARQ scrapie. Thus, direct neuroinvasion, apparently without a prior phase of replication in the lymphoreticular system, occurred in a proportion of VRQ/ARQ sheep. Possibly it may occur in all sheep of the VRQ/ARR genotype. The factors responsible for direct neuroinvasion are not understood. However, it cannot be attributed to genotype alone.

Animals↗
PubMed2002

A murine interleukin-4-Ig fusion protein regulates the expression of Th1- and Th2-specific cytokines in the pancreas of NOD mice.

Interleukin (IL)-4 is a key cytokine in T-helper type 2 (Th2) immune response. We have constructed a dimeric IL-4 molecule consisting of the murine IL-4 and the murine Fc part of IgG2a. We first tested the biological activity of the chimeric protein by in vitro studies using isolated murine spleen cells. IL-4-Ig was found to downregulate LPS-induced IFN-gamma and TNF-alpha production. The immunomodulatory potential of the fusion protein was also analyzed in non-obese diabetic (NOD) mice, an animal model for human type 1 diabetes. Female NOD mice aged 10 weeks were treated once with cyclophosphamide to accelerate and synchronize the progression of insulitis. Treatment with IL-4-Ig induced strong modulation of the pancreatic cytokine balance. Expression was downregulated for both Th1-specific cytokine IFN-gamma and the Th2-specific cytokine IL-10. IL-12p40 expression was only slightly affected. Interestingly, infiltration increased in the islets of IL-4-Ig-treated animals, and therefore did not correlate with the decreased IFN-gamma expression. Hence, IL-4-Ig did not prevent the progression from peri- to intra-insulitis, but suppressed inflammatory cytokine production. In most experiments, the biological activity of IL-4-Ig and IL-4 was comparable. We conclude that treatment with the chimeric protein IL-4-Ig effectively downregulates Th1 responses but simultaneously augments intra-islet infiltration.

Animals↗
PubMed2002

Short compared with standard duration of antibiotic treatment for urinary tract infection: a systematic review of randomised controlled trials.

AIMS: To compare the effectiveness of short course (2-4 days) with standard duration oral antibiotic treatment (7-14 days) for urinary tract infection (UTI). METHODS: Meta-analysis of randomised controlled trials using a random effects model. Ten trials were eligible, involving 652 children with lower tract UTI recruited from outpatient or emergency departments. Main outcome measures were UTI at the end of treatment, UTI during follow up (recurrent UTI), and urinary pathogens resistant to the treating antibiotic. RESULTS: There was no significant difference in the frequency of positive urine cultures between the short (2-4 days) and standard duration therapy (7-14 days) for UTI in children at 0-7 days after treatment (eight studies: RR 1.06; 95% CI 0.64 to 1.76) and at 10 days to 15 months after treatment (10 studies: RR 1.01; 95% CI 0.77 to 1.33). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (one study: RR 0.57, 95% CI 0.32 to 1.01) or in recurrent UTI (three studies: RR 0.39, 95% CI 0.12 to 1.29). CONCLUSION: A 2-4 day course of oral antibiotics is as effective as 7-14 days in eradicating lower tract UTI in children.

Adolescent↗
PubMed2002

User satisfaction with home telecare based on broadband communication.

Home telecare services based on broadband communication were established in five locations in Europe. Two different types of telecare unit were developed: one based on a PC or set-top box containing a videoconferencing codec and another on off-the-shelf videoconferencing units. The participants in the project were 13 medical staff, 135 patients and 88 people informally caring for the patients. Questionnaires were used to evaluate user satisfaction with eight telecare services. Almost all participants rated the usability of the system as good or excellent. A total of 105 telecare sessions were scored by the medical staff. Overall, the quality of audio and video communication was judged satisfactory. For the patients and carers, the perceived quality of communication was also satisfactory and did not vary significantly between sites. The medical staff were reasonably satisfied with how the service supported them in their work. Except for the item about being able to support patients in a critical situation, medical staff agreed that an improved quality of health services was offered through telecare. All participants agreed that personal information was treated confidentially and that there was little risk in using the telecare services. The medical staff trusted the assessments they could make remotely while using the telecare system. Although the findings cannot be generalized due to the small number of telecare sessions and the relatively short duration of the experiment, the results encourage further research.

Adolescent↗
PubMed2002

[Pulmonary tuberculosis presenting as tubercular lupus].

Pulmonary tuberculosis can be associated with skin manifestations. We report a case in which cutaneous tuberculous lesions were associated with asymptomatic pulmonary tuberculosis. A 15-year old woman had four cutaneous tumoral lesions on her face back, a few of which had evolved over a period of several years. They were asymptomatic nodular lesions, with rounded bumps, with, in places, cheloidal features. The biopsy specimen revealed non-caseating epithelioid granulomas with giant cells and the culture grew Mycobacterium tuberculosis. Cavitating pulmonary tuberculosis was then revealed by CT scan and acid-fast bacilli were isolated in her sputum. The skin lesions disappeared with anti-tuberculosis therapy. Cutaneous manifestations of tuberculosis are rare, polymorphous, and can be associated with an underlying visceral infection. Lupus vulgaris is the most common cutaneous manifestation of tuberculosis in industrialised countries, but nevertheless it remains rare and it is a very unusual presenting feature of underlying pulmonary tuberculosis.

Adolescent↗
PubMed2002

[Neurosurgical and endovascular treatment of intracranial aneurysms: a cost analysis of two different strategies at the University Hospital of Bordeaux (France)].

BACKGROUND: Rupture of intracranial aneurysms causes major mortality and morbidity. Moreover, treatment of this vascular malformation generates high medical costs. We compared the cost of two different strategies employed at the University of Bordeaux to prevent aneurysms from rebleeding: a classical neurosurgical technique consisting in clipping the neck of the aneurysm and a new less invasive neuroradiological technique based on embolization using platinum coils. METHOD: A micro-cost study was carried out retrospectively from May 1998 to June 2000) comparing data from 44 patients admitted for ruptured intracranial aneurysm: 22 operated patients and 22 patients treated with an endovascular approach. Each operated patient was matched with an embolized patient for clinical status at admission (World Federation of Neurological Surgeons Scale) and complications resulting from cerebral hemorrhage (hydrocephalus, vasospasm, rebleeding). RESULTS AND CONCLUSION: Our results showed the same cost for the same efficiency . Expenditures are however made differently. The endovascular technique allows a shorter hospital stay (8 days less), balancing the high cost of single use medical supplies (coils, microcatheters.). The endovascular technique has many advantages for the patients, but cannot be successful in all types of intracranial aneurysms. Both techniques remain indispensable.

Aneurysm, Ruptured↗
PubMed2001

Deposition of the NG2 proteoglycan at nodes of Ranvier in the peripheral nervous system.

The node of Ranvier is a complex macromolecular assembly of ion channels and other proteins that is specialized for the rapid propagation of the action potential. A full understanding of the processes responsible for the assembly and maintenance of the node requires first the identification and characterization of the proteins found there. Here we show that NG2, a structurally unique chondroitin sulfate proteoglycan, is a molecular component of the node of Ranvier in the peripheral nervous system. In adult sciatic nerve, NG2 is (1) associated with thin, elongated fibroblast-like cells, (2) on some but not all basal laminae, and (3) at nodes of Ranvier. At the nodes, NG2 is restricted to the nodal gap and is absent from the paranodal or juxtaparanodal region. In dissociated cell cultures of adult sciatic nerve, perineurial fibroblasts but not Schwann cells express NG2 on their surfaces. Approximately 45% of the total NG2 in peripheral nerves is in a soluble, rather than particulate, subcellular compartment. NG2 is also present in membrane fractions that also contain high levels of voltage-dependent sodium channels, caspr, and neuron-glia related cell adhesion molecule. These medium-density membranes likely correspond to the nodal and paranodal region of the axon-Schwann cell unit. These results suggest a model in which perineurial fibroblasts secrete or shed NG2, which subsequently associates with nodes of Ranvier. The growth-inhibitory and anti-adhesive properties of NG2 may limit the lateral extension of myelinating Schwann cells as nodes mature. NG2 may also participate in the barrier functions of the perineurial linings of the nerve.

Animals↗
PubMed2001

Point mutation in the stalk of angiotensin-converting enzyme causes a dramatic increase in serum angiotensin-converting enzyme but no cardiovascular disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) metabolizes many small peptides and plays a key role in blood pressure regulation. Elevated serum ACE is claimed to be associated with an increased risk for cardiovascular disease. Previously, two families with dramatically increased serum ACE were described, but no systematic survey of affected individuals was performed, and the molecular background of this trait is unknown. METHODS AND RESULTS: Eight families were identified with autosomal dominant inheritance of a dramatic (5-fold) increase of serum ACE activity. Strikingly, no clinical abnormalities were apparent in the affected subjects. Isolated blood cells were used for genetic and biochemical analysis. The level of ACE expression on the blood leukocytes and dendritic cells and total cell-associated ACE of the affected individuals was similar to that in nonaffected relatives; however membrane-bound mutant ACE was much more efficiently clipped from the cell surface compared with its wild-type counterpart. A point mutation causing Pro1199Leu in the stalk region of the ACE molecule cosegregates with the increase in serum ACE (LOD score, 6.63). CONCLUSIONS: A point mutation in the stalk region of the ACE protein causes increased shedding, leading to increased serum ACE, whereas cell-bound ACE is unaltered, and affected individuals exhibit no clinical abnormalities. These findings qualify the importance of serum ACE and establish a new determinant of ACE solubilization.

Adult↗
PubMed2001

Dicubane-like tetrameric cobalt(II)-pseudohalide ferromagnetic clusters.

Three tetrameric cobalt(II)-pseudohalide complexes have been structurally and magnetically characterized. Compounds 1 and 2 are isomorphous and exhibit the general formula [Co2(dpk-OH)(dpk-CH3O)(L)(H2O)]2A2-4H2O where dpk = di-2-pyridyl ketone, L = N3(-) and A = BF4(-) for 1, and L = NCO(-) and A = ClO4(-) for 2. The ligands dpk-OH(-) and dpk-CH3O(-) result from solvolysis and ulterior deprotonation of dpk in water and methanol, respectively. Both compounds exhibit cationic tetramers consisting of a dicubane-like core with two missing vertexes where the Co(II) ions are connected through end-on pseudohalide and oxo-bridges. A similar tetranuclear core has been found for 3 whose formula is [Co2(dpk-OH)(dpk-CH3O)(NCO)2]2. In this case, the tetramers are neutral and exhibit a terminal cyanate in place of the coordinated molecule of water for 1 and 2. The tetrameric units for 2 and 3 represent the first examples of any kind of cubanes exhibiting cyanate bridges as well as the first Co(II) compounds exhibiting intermetallic bridges through these pseudohalide groups. Measurements of the magnetic susceptibility indicated the presence of ferromagnetic Co(II)-Co(II) interactions in the three compounds.

Journal Article↗
PubMed2001

IgG antibody subclass responses determined by immunoblot in infants' sera following vaccination with a meningococcal recombinant hexavalent PorA OMV vaccine.

The introduction of meningococcal serogroup C conjugate vaccines into the UK immunisation schedule has led to the decline of serogroup C disease in those vaccinated but there is no imminent vaccine solution for serogroup B disease. The PorA outer membrane protein (OMP) is a potential serogroup B vaccine candidate and an outer membrane vesicle (OMV) vaccine containing six different PorA OMPs (each representing a different serosubtype) has been evaluated in phase II trials with encouraging results. Little is known about the IgG subclass response to the various antigens contained within this vaccine. These responses are important due to the different half-lives and complement fixing abilities of these antibodies. In this study, immunoblotting was undertaken with infants' sera following either three or four doses of vaccine, and OMVs from six isogenic meningococcal strains differing only in their PorA serosubtype. Following either three or four doses of the vaccine, IgG(3) and IgG(1) subclass antibodies were induced to all six of the isogenic strains, although sera collected after four doses of vaccine showed stronger antibody levels. IgG(3) was found in more sera than IgG(1). For both sets of sera, the two isogenic strains expressing P1.5,2 and P1.5(c),10 induced stronger IgG subclass antibody responses than the other four meningococcal strains. The recombinant hexavalent PorA OMV vaccine stimulates both IgG(1) and IgG(3) subclass antibodies, the subclasses that are most effective in activating the complement system.

Electrophoresis, Polyacrylamide Gel↗
PubMed2001

A predictive test for the efficacy of intravenous immunoglobulin in the inhibition of alloantibodies.

Preformed recipient HLA-specific antibodies can cause hyperacute rejection of a transplanted kidney if they are directed against mismatched donor HLA antigens. To avoid hyperacute rejection it is essential that recipient antibodies be identified during patient workup for transplantation and HLA antigens to which a patient is sensitized then be avoided when selecting a kidney donor for them. Absence of donor-specific reactivity is then confirmed by a pretransplantation crossmatch test.

HLA Antigens↗
PubMed2001

The role of Ca2+ in insulin-stimulated glucose transport in 3T3-L1 cells.

We have examined the requirement for Ca2+ in the signaling and trafficking pathways involved in insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Chelation of intracellular Ca2+, using 1,2-bis (o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra (acetoxy- methyl) ester (BAPTA-AM), resulted in >95% inhibition of insulin-stimulated glucose uptake. The calmodulin antagonist, W13, inhibited insulin-stimulated glucose uptake by 60%. Both BAPTA-AM and W13 inhibited Akt phosphorylation by 70-75%. However, analysis of insulin-dose response curves indicated that this inhibition was not sufficient to explain the effects of BAPTA-AM and W13 on glucose uptake. BAPTA-AM inhibited insulin-stimulated translocation of GLUT4 by 50%, as determined by plasma membrane lawn assay and subcellular fractionation. In contrast, the insulin-stimulated appearance of HA-tagged GLUT4 at the cell surface, as measured by surface binding, was blocked by BAPTA-AM. While the ionophores or ionomycin prevented the inhibition of Akt phosphorylation and GLUT4 translocation by BAPTA-AM, they did not overcome the inhibition of glucose transport. Moreover, glucose uptake of cells pretreated with insulin followed by rapid cooling to 4 degrees C, to promote cell surface expression of GLUT4 and prevent subsequent endocytosis, was inhibited specifically by BAPTA-AM. This indicates that inhibition of glucose uptake by BAPTA-AM is independent of both trafficking and signal transduction. These data indicate that Ca2+ is involved in at least two different steps of the insulin-dependent recruitment of GLUT4 to the plasma membrane. One involves the translocation step. The second involves the fusion of GLUT4 vesicles with the plasma membrane. These data are consistent with the hypothesis that Ca2+/calmodulin plays a fundamental role in eukaryotic vesicle docking and fusion. Finally, BAPTA-AM may inhibit the activity of the facilitative transporters by binding directly to the transporter itself.

3T3 Cells↗