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Biomedical subjects

I Martin

Publications and source records attributed to I Martin.

At least 73 records · Page 4Linked to original sources
PubMed2001

Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints.

OBJECTIVE: To quantify the expression of genes encoding extracellular matrix (ECM) proteins in human cartilage from normal and osteoarthritic (OA) joints. DESIGN: Human cartilage samples were classified as control (CTR) or OA according to clinical evaluation and assessed histologically and biochemically to confirm the diagnosis. mRNAs encoding collagen types I, II and X, aggrecan, versican, osteopontin and osteocalcin were quantified by real-time reverse transcription-PCR assays and normalized to a reference mRNA (GAPDH). RESULTS: RNA from native cartilage could be reproducibly and efficiently amplified by real-time PCR only if isolated using purification membranes. Primers and fluorescent probes for real-time PCR, endowed with comparable (<6% difference from GAPDH) and high (>91%) amplification efficiencies, were designed and validated for the selected ECM genes. The expression of most genes under investigation displayed large variations and was not significantly different in CTR and OA cartilage. Only osteopontin mRNA levels were significantly higher in OA than CTR specimens. mRNA ratios of collagen type II to I and of aggrecan to versican, defined as indexes of chondrocyte differentiation, were less variable within each population than the single genes and markedly higher (27.0 and 7.6-fold, respectively) in CTR than OA cartilage, with high statistical significance (P = 0.00013 and P = 0.00007, respectively). CONCLUSIONS: Our results provide evidence that gene patterns related to chondrocyte differentiation discriminate between CTR and OA human cartilage with higher sensitivity than single ECM genes. The method described here has the potential to improve understanding of the progression of OA and could become a valuable diagnostic tool.

Adult↗
PubMed2000

A prospective social and molecular investigation of gonococcal transmission.

BACKGROUND: Gonorrhoea is a common infectious disease, poorly controlled despite effective treatments. Tracing chains of transmission is difficult, because sexual partners are commonly difficult or impossible to identify. We assess the use of gonococcal opa-typing in identifying transmission links not revealed through interview. METHODS: Epidemiological data and gonococcal isolates were collected prospectively from patients at two UK clinics in London and Sheffield. Social and epidemiological data were combined with molecular typing of gonococcal isolates by a new methodology based on the polymorphisms of the opa gene. FINDINGS: In London, interview data and opa-typing on samples from 215 cases showed a diverse population with few links. In Sheffield, interview data identified links between 51 (43%) of 120 cases, whereas opa-typing suggested a more connected population: 95 (79%) of cases had shared profiles. There was a highly significant correlation between the two distributions with epidemiological clusters appearing as a subset of the opa clusters. Two large opa clusters, of 18 and 43 cases, accounted for 50% of local cases of gonorrhoea. Discordance between epidemiological and opa-typing data was observed at highly connected points in the sexual network. INTERPRETATION: Opa-typing is a more powerful tool for epidemiological investigation of gonorrhoea transmission than earlier methods. Opa-typing can link infections that would otherwise remain unlinked, and may aid interventions to control endemic disease.

Adolescent↗
PubMed2000

Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones.

The ability of marrow-derived osteoprogenitor cells to promote repair of critical-size tibial gaps upon autologous transplantation on a hydroxyapatite ceramic (HAC) carrier was tested in a sheep model. Conditions for in vitro expansion of sheep bone marrow stromal cells (BMSC) were established and the osteogenic potential of the expanded cells was validated. Ectopic implantation of sheep BMSC in immunocompromised mice led to extensive bone formation. When used to repair tibial gaps in sheep, cell-loaded implants (n = 2) conducted a far more extensive bone formation than did cell-free HAC cylinders (n = 2) over a 2-month period. In cell-loaded implants, bone formation was found to occur both within the internal macropore space and around the HAC cylinder while in control cell-free implants, bone formation was limited mostly to the outer surface and was not observed in most of the inner pores. As tested in an indentation assay, the stiffness of the complex HAC-bone material was found to be higher in cell-loaded implants compared to controls. Our pilot study on a limited number of large-sized animals suggests that the use of autologous BMSC in conjunction with HAC-based carriers results in faster bone repair compared to HAC alone. Potentially this combination could be used clinically in the treatment of extensive long bone defects.

Animals↗
PubMed2000

Macroporous polymer foams by hydrocarbon templating.

Porous polymeric media (polymer foams) are utilized in a wide range of applications, such as thermal and mechanical insulators, solid supports for catalysis, and medical devices. A process for the production of polymer foams has been developed. This process, which is applicable to a wide range of polymers, uses a hydrocarbon particulate phase as a template for the precipitation of the polymer phase and subsequent pore formation. The use of a hydrocarbon template allows for enhanced control over pore structure, porosity, and other structural and bulk characteristics of the polymer foam. Polymer foams with densities as low as 120 mg/cc, porosity as high as 87%, and high surface areas (20 m(2)/g) have been produced. Foams of poly(l-lactic acid), a biodegradable polymer, produced by this process have been used to engineer a variety of different structures, including tissues with complex geometries such as in the likeness of a human nose.

Biocompatible Materials↗
PubMed2000

Protein-induced fusion can be modulated by target membrane lipids through a structural switch at the level of the fusion peptide.

Regulatory features of protein-induced membrane fusion are largely unclear, particularly at the level of the fusion peptide. Fusion peptides being part of larger protein complexes, such investigations are met with technical limitations. Here, we show that the fusion activity of influenza virus or Golgi membranes is strongly inhibited by minor amounts of (lyso)lipids when present in the target membrane but not when inserted into the viral or Golgi membrane itself. To investigate the underlying mechanism, we employ a membrane-anchored peptide system and show that fusion is similarly regulated by these lipids when inserted into the target but not when present in the peptide-containing membrane. Peptide-induced fusion is regulated by a reversible switch of secondary structure from a fusion-permissive alpha-helix to a nonfusogenic beta-sheet. The "on/off" activation of this switch is governed by minor amounts of (lyso)-phospholipids in targets, causing a drop in alpha-helix and a dramatic increase in beta-sheet contents. Concomitantly, fusion is inhibited, due to impaired peptide insertion into the target membrane. Our observations in biological fusion systems together with the model studies suggest that distinct lipids in target membranes provide a means for regulating membrane fusion by causing a reversible secondary structure switch of the fusion peptides.

Animals↗
PubMed2000

Finite-temperature density instability at high landau level occupancy

We study here the onset of charge density wave instabilities in quantum Hall systems at finite temperature for Landau level filling nu>4. Specific emphasis is placed on the role of disorder as well as on an in-plane magnetic field. Beyond some critical value, disorder is observed to suppress the charge density wave melting temperature to zero. In addition, we find that a transition from perpendicular to parallel stripes (relative to the in-plane magnetic field) exists when the electron gas thickness exceeds approximately 60 A. The perpendicular alignment of the stripes is in agreement with the experimental finding that the easy conduction direction is perpendicular to the in-plane field.

Journal Article↗
PubMed2000

In vitro generation of osteochondral composites.

Osteochondral repair involves the regeneration of articular cartilage and underlying bone, and the development of a well-defined tissue-to-tissue interface. We investigated tissue engineering of three-dimensional cartilage/bone composites based on biodegradable polymer scaffolds, chondrogenic and osteogenic cells. Cartilage constructs were created by cultivating primary bovine calf articular chondrocytes on polyglycolic acid meshes; bone-like constructs were created by cultivating expanded bovine calf periosteal cells on foams made of a blend of poly-lactic-co-glycolic acid and polyethylene glycol. Pairs of constructs were sutured together after 1 or 4 weeks of isolated culture, and the resulting composites were cultured for an additional 4 weeks. All composites were structurally stable and consisted of well-defined cartilaginous and bone-like tissues. The fraction of glycosaminoglycan in the cartilaginous regions increased with time, both in isolated and composite cultures. In contrast, the mineralization in bone-like regions increased during isolated culture, but remained approximately constant during the subsequent composite culture. The integration at the cartilage/bone interface was generally better for composites consisting of immature (1-week) than mature (4-week) constructs. This study demonstrates that osteochondral tissue composites for potential use in osteochondral repair can be engineered in vitro by culturing mammalian chondrocytes and periosteal cells on appropriate polymer scaffolds.

Animals↗
PubMed2000

Severe menorrhagia due to Glanzmann thrombasthenia treated with hydrothermal ablation.

Glanzmann thrombasthenia is a rare platelet disorder inherited as an autosomal recessive trait. Abnormal uterine bleeding is a common problem in women with the disease. Medical management may not always be effective and further treatment may be necessary. Two women underwent endometrial ablation with a continuous-flow circulating hydrothermal ablator. After follow-up of 12 and 18 months, both women remained without abnormal uterine bleeding.

Adolescent↗
PubMed2000

Common properties of fusion peptides from diverse systems.

Although membrane fusion occurs ubiquitously and continuously in all eukaroytic cells, little is known about the mechanism that governs lipid bilayer fusion associated with any intracellular fusion reactions. Recent studies of the fusion of enveloped viruses with host cell membranes have helped to define the fusion process. The identification and characterization of key proteins involved in fusion reactions have mainly driven recent advances in our understanding of membrane fusion. The most important denominator among the fusion proteins is the fusion peptide. In this review, work done in the last few years on the molecular mechanism of viral membrane fusion will be highlighted, focusing in particular on the role of the fusion peptide and the modification of the lipid bilayer structure. Much of what is known regarding the molecular mechanism of viral membrane fusion has been gained using liposomes as model systems in which the molecular components of the membrane and the environment are strictly controlled. Many amphilphilic peptides have a high affinity for lipid bilayers, but only a few sequences are able to induce membrane fusion. The presence of alpha-helical structure in at least part of the fusion peptide is strongly correlated with activity whereas, beta-structure tends to be less prevalent, associated with non-native experimental conditions, and more related to vesicle aggregation than fusion. The specific angle of insertion of the peptides into the membrane plane is also found to be an important characteristic for the fusion process. A shallow penetration, extending only to the central aliphatic core region, is likely responsible for the destabilization of the lipids required for coalescence of the apposing membranes and fusion.

ADAM Proteins↗
PubMed2000

Mucinous cystic neoplasms of the pancreas: imaging features and diagnostic difficulties.

AIMS: To review the imaging features of mucinous cystic neoplasms (MCNs) of the pancreas and to highlight difficulties in differentiating these lesions from pancreatic pseudocysts. MATERIALS AND METHODS: The imaging investigations, case notes and histopathology of 13 patients who underwent surgery for an MCN of the pancreas, were reviewed. RESULTS: An erroneous diagnosis of a pancreatic pseudocyst had been made in five of the 13 cases and in two patients cystenterostomy had been performed. Only one patient had a documented history of acute pancreatitis although mildly elevated serum amylase levels were identified in a further five cases. CT and US correctly diagnosed a cystic pancreatic mass in all 13 patients, however cross-sectional imaging features of neoplasia, such as septae, cyst wall calcification, focal thickening of the cyst wall and papillary projections, were absent in five (38%) cases. Coexistent imaging features of chronic pancreatitis were present in five of the 13 patients and in six resected specimens. Cyst wall calcification occurred only in malignant lesions and there was no relationship between cyst size and the degree of malignancy. While ERCP, angiography, and percutaneous needle aspiration may provide additional information, the majority of these examinations were either unhelpful or even misleading. CONCLUSION: MCNs of the pancreas are frequently diagnosed and mismanaged as pancreatic pseudocysts with an associated increase in patient morbidity and mortality. Diagnostic imaging can help to distinguish MCNs from pseudocysts when there are features of neoplasia present, however, no imaging investigation can reliably differentiate the two conditions in all cases. If clinical doubt remains, it is preferable to err on the side of safety and either employ a 'wait and watch' strategy or to resect a cystic pancreatic lesion rather than drain a potentially malignant MCN.

Adult↗
PubMed2000

Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors.

The increasing incidence of life-threatening fungal infections has driven the search for new, broad-spectrum fungicidal agents that can be used for treatment and prophylaxis in immunocompromised patients. Natural-product inhibitors of cell wall (1,3)-beta-D-glucan synthase such as lipopeptide pneumocandins and echinocandins as well as the glycolipid papulacandins have been evaluated as potential therapeutics for the last two decades. As a result, MK-0991 (caspofungin acetate; Cancidas), a semisynthetic analogue of pneumocandin B(o), is being developed as a broad-spectrum parenteral agent for the treatment of aspergillosis and candidiasis. This and other lipopeptide antifungal agents have limited oral bioavailability. Thus, we have sought new chemical structures with the mode of action of lipopeptide antifungal agents but with the potential for oral absorption. Results of natural-product screening by a series of newly developed methods has led to the identification of four acidic terpenoid (1,3)-beta-D-glucan synthase inhibitors. Of the four compounds, the in vitro antifungal activity of one, enfumafungin, is comparable to that of L-733560, a close analogue of MK-0991. Like the lipopeptides, enfumafungin specifically inhibits glucan synthesis in whole cells and in (1,3)-beta-D-glucan synthase assays, alters the morphologies of yeasts and molds, and produces a unique response in Saccharomyces cerevisiae strains with point mutations in FKS1, the gene which encodes the large subunit of glucan synthase.

Antifungal Agents↗
PubMed2000

Comparative intracellular cytokine production by in vitro stimulated T lymphocytes from human umbilical cord blood (HUCB) and adult peripheral blood (APB).

To date over 400 HUCB transplants have been reported from different centers. It has been suggested that there is a reduced graft-versus-host-disease (GVHD) with HUCB compared to bone marrow transplantation. Since cytokine production by a cell is an indication of the cells function it is important to determinate the differences between APB and HUCB with respect to production of these soluble factors. Our aim was to analyse the intracellular cytokine production by HUCB and APB T lymphocytes with and emphasize on their possible role in GVHD. Heparinized HUCB samples from 8 normal full-term deliveries and 10 normal blood donors were stimulated 4 hours at 37 degrees C and 5% CO2 with phorbol 12-myristate 13-acetate (PMA) and lonomycin in the presence of brefeldine. Afterwards cells were stained with CD3, CD4 or CD8 in different combinations. Finally, after cell permeabilization, cells were stained with Il-2, Il-4 or IFN-gamma. Data acquisition was performed on a FACScan flow cytometer. Compared to APB, HUCB T lymphocytes produced less Il-2, Il-4 and IFN-gamma. In HUCB, Il-2, Il-4 and IFN-gamma were produced predominantly by CD4+ T cells. In APB, Il-2 and Il-4 were also produced predominantly by CD4+ cells compared with CD8+ T lymphocytes, however, IFN-gamma was produced by both CD4+ and CD8+ T cells. These results indicate that there are clear differences in the cytokine profile between T cells in APB and HUCB.

Adult↗
PubMed2000

Neisseria gonorrhoeae in a London sexually transmitted infection clinic not fully sensitive to quinolones: are isolates imported and how effective is ciprofloxacin as a first-line therapy?

Our objectives were to determine the prevalence of Neisseria gonorrhoeae not fully sensitive to ciprofloxacin from a sexually transmitted infection (STI) clinic in London and where the isolates were acquired from. Data of antibiotic sensitivities of N. gonorrhoeae from 292 patients were reviewed over a 6-month period at St Mary's Genitourinary Medicine (GUM) Clinic, London. Isolates which exhibited reduced susceptibility (minimum inhibitory concentration [MIC] 0.03-0.12 mg/l) and high level resistance (MIC>0.12 mg/l) to ciprofloxacin represented 10% and 1.3% of the total respectively. All patients infected with a high level resistant isolate to ciprofloxacin had had a recent sexual partner from abroad but 18 of the 28 patients infected with a reduced susceptibility isolate denied recent travel. None of the 20 patients with a non-sensitive isolate who re-attended for post treatment cultures had persistant gonococcal infection. From this study we concluded that although N. gonorrhoeae resistant to ciprofloxacin was rare and probably always acquired abroad, isolates exhibiting reduced susceptibility were more common and were mainly as a result of infection from the UK. A stat dose of ciprofloxacin 500 mg and doxycycline 100 mg twice a day for one week was effective treatment.

Adolescent↗