Biomedical subjects

H S Gill

Publications and source records attributed to H S Gill.

At least 37 records · Page 2Linked to original sources

PubMed2005

Inability of probiotic bacterial strains Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019 to induce human platelet aggregation in vitro.

Platelet aggregation contributes to the pathogenesis of infective endocarditis, and aggregation of platelets induced by lactobacilli is thought to be an important contributory factor in the development and progression of Lactobacillus endocarditis. The main purpose of this study was to examine the effect of immunity-enhancing probiotic strains Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019 on the activation and aggregation of human blood platelets. Whole blood samples from healthy individuals were incubated in vitro with HN001 or HN019 and subsequently labeled with platelet-specific monoclonal antibodies, fluorescein isothiocyanate-conjugated anti-CD41a (expressed on normal platelets), and phycoerythrin-streptavidin-conjugated anti-CD62p (expressed on activated platelets) before analysis by flow cytometry. Platelet-rich plasma was used to assist the gating of the platelet cluster. ADP and epinephrine were used as the physiological platelet activation agonists. Platelet aggregation-inducing strain Streptococcus sanguis 133-79 was used as a positive control strain. The mean fluorescence intensity of phycoerythrin and the percentage of platelets expressing the CD62p marker were used to assess the degree of platelet activation. The percentage of CD62p-positive platelets and the light scatter profiles of the agonist-activated platelets were used to identify the occurrence and degree of platelet aggregation. HN001 and HN019 had no effect on spontaneous platelet activation and aggregation; they also failed to exacerbate the platelet aggregation activity induced by ADP and epinephrine. Therefore, these test probiotic strains HN001 and HN019 are less likely to participate in the pathogenesis of infective endocarditis or other thrombotic disorders with regard to platelet aggregation factors.

Antibodies, Monoclonal↗

PubMed2004

Accurate assessment of patellar tracking using fiducial and intensity-based fluoroscopic techniques.

Accuracies of a point-based and an intensity-based fluoroscopic methods of assessing patella tracking were determined by comparing the pattern of patellar motion with respect to orientation (flexion, internal rotation, and lateral tilt) and translation (lateral, proximal, and anterior) with the pattern of patellar motion measured using Roentgen stereophotogrammetric analysis in three cadaver knee specimens. Each pose in the patellar motion could be obtained from single as well as multiple calibrated fluoroscopic images. The errors using the intensity-based method were slightly higher than those of the point-based method, but they appear to be sufficiently low to detect clinically significant differences in patellar kinematics.

Adult↗

PubMed2004

In vivo measurement of total knee replacement wear.

Polyethylene wear is one of the most important causes of failure of total knee replacements (TKRs). Currently, wear can only be accurately measured by retrieval studies. There is a need for a method to measure wear accurately in vivo. We have developed a Roentgen stereophotogrammetric analysis (RSA) system that can measure penetration of the metallic femoral component into the polyethylene of the tibia. We have used this system to study six AGC TKRs at 6 years postoperatively and six control AGC TKRs at 2 weeks postoperatively. The mean difference between the RSA measured bearing thickness and the manufacturer's quoted values for the control group was -0.03 mm (S.D. 0.17). The average linear penetration in the study group was 0.8 mm (S.D. 0.46). This was significantly (P<0.0001) different from the control group. The average linear penetration rate was 0.13 mm per year (S.D. 0.08). We would expect the penetration to deepen with time. In young active patients, this could be a cause for concern, particularly with a thin bearing. The current system is accurate enough to measure wear at 5 years post TKR. It has the potential for predicting long-term wear problems with new designs of TKR and new materials within 2 years.

Aged↗

PubMed2004

Probiotics and human health: a clinical perspective.

There is unequivocal evidence that administration of probiotics could be effective in the treatment of acute infectious diarrhoea in children and the prevention of antibiotic associated diarrhoea and nosocomial/community acquired diarrhoea. Encouraging evidence is also emerging for the effectiveness of probiotics in the prevention and management of pouchitis and paediatric atopic diseases, and the prevention of postoperative infections. There is also strong evidence that certain probiotic strains are able to enhance immune function, especially in subjects with less than adequate immune function such as the elderly. Efficacy of probiotics in the prevention of traveller's diarrhoea, sepsis associated with severe acute pancreatitis, and cancers, the management of ulcerative colitis, and lowering of blood cholesterol remains unproven. In addition to firm evidence of efficacy (for a range of conditions), major gaps exist in our knowledge regarding the mechanisms by which probiotics modulate various physiological functions and the optimum dose, frequency, and duration of treatment for different probiotic strains.

Bacterial Infections↗

PubMed2004

Roentgen stereophotogrammetric analysis of the Birmingham hip resurfacing arthroplasty. A two-year study.

The Birmingham hip resurfacing (BHR) arthroplasty is a metal-on-metal prosthesis for which no medium- or long-term results have been published. Despite this, it is increasing in popularity as an alternative to stemmed prostheses for younger patients. Since the fixation of the socket is conventional, the major concern is long-term failure of the femoral component. This can be predicted by the use of roentgen stereophotogrammetric analysis (RSA). We have therefore undertaken such a study of the BHR femoral component over a period of two years. Twenty patients (22 hips) underwent a standard BHR procedure. Migration of the femoral component was measured by RSA at intervals of three, six, 12 and 24 months. At 24 months the total three-dimensional migration of the head was 0.2 mm. This was not statistically significant. Previous studies have shown that implants which loosen quickly have rapid early migration. Our results therefore suggest that the BHR femoral component is an inherently stable device which is likely to perform well in the long term.

Adult↗

PubMed2003

The influence of cement viscosity on the early migration of a tapered polished femoral stem.

It is unclear whether it is best to use high-viscosity or low-viscosity cement for fixation of total hip replacement (THR) femoral components. This study examines the influence of cement viscosity on the migration of the Exeter femoral component using roentgen stereophotogrammetric analysis (RSA). Simplex, CMW1 and CMW3 G cements were examined in a total of 46 patients over a 12-month period. The overall pattern of migration for all cohorts was one of subsidence and rotation into valgus. There was no significant difference in any aspect of migration between the groups. In vitro studies demonstrate that low-viscosity cement forms a more stable bone-cement interface. Several groups have examined the in vivo effect of cement viscosity on stem longevity with conflicting results. For a polished, tapered implant that is designed to subside, cement viscosity does not influence the 1-year migration, and it is therefore unlikely to affect long-term outcome.

Aged↗

PubMed2003

Heelstrike and the pathomechanics of osteoarthrosis: a pilot gait study.

Involvement of mechanical factors in osteoarthrosis (OA) has been well documented. For OA of the human lower limb, the impulse imparted at heelstrike has been suggested as a pathogenic factor. It has also been reported that there is a large amount of variation in the level of impulse experienced by different individuals, and it is suggested that those who experience large impulses are at a greater risk of developing OA. The current study investigated gait patterns of 12 normal subjects to establish the gait determinants responsible for producing large impulses at heelstrike. The results suggest that subtle variations in the early part of the swing phase pattern are responsible for large differences in the impulse experienced at heelstrike; the usually reported gait variables mask these variations.

Acceleration↗

PubMed2003

Heelstrike and the pathomechanics of osteoarthrosis: a simulation study.

A simulation model and trajectory matching method were developed to investigate the differences between two swing phase gait patterns; one giving rise to a large impulse at heelstrike, the other giving a small impulse. Subtle changes in the kinematics of the swing leg dramatically reduced the vertical contact velocity of the ankle at the moment of heelstrike. Phasing of the hip flexor muscles at the start of swing was responsible for the level of impulse observed at heelstrike.

Adaptation, Physiological↗

PubMed2003

The TB structural genomics consortium: a resource for Mycobacterium tuberculosis biology.

The TB Structural Genomics Consortium is an organization devoted to encouraging, coordinating, and facilitating the determination and analysis of structures of proteins from Mycobacterium tuberculosis. The Consortium members hope to work together with other M. tuberculosis researchers to identify M. tuberculosis proteins for which structural information could provide important biological information, to analyze and interpret structures of M. tuberculosis proteins, and to work collaboratively to test ideas about M. tuberculosis protein function that are suggested by structure or related to structural information. This review describes the TB Structural Genomics Consortium and some of the proteins for which the Consortium is in the progress of determining three-dimensional structures.

Amino Acid Sequence↗

PubMed2003

Effect of dietary whey protein concentrate on primary and secondary antibody responses in immunized BALB/c mice.

Proteins derived from the whey fraction of bovine milk are known to modulate immune responses. We have previously described a rennet whey protein concentrate (WPC) that can boost intestinal tract antibody responses to orally administered T-dependent antigens. In the present study, we investigated the effects of feeding WPC to mice on specific antibody responses to several orally or parenterally administered antigens, including influenza vaccine, diphtheria and tetanus toxoids, poliomyelitis vaccine, ovalbumin and cholera toxin sub-unit. WPC-fed mice produced elevated levels of antigen-specific intestinal tract and serum antibodies against all tested antigens, compared to mice that were fed a standard chow diet. Both primary and secondary intestinal tract antibody responses were elevated by WPC feeding, while only secondary serum responses were increased in WPC-fed mice. Significant up-regulation of intestinal tract antibody was observed within 2 weeks of primary oral immunizations. A period of pre-feeding with WPC, prior to commencement of immunization, did not alter the kinetics or magnitude of immune enhancement. These results identify bovine WPC as a potentially important dietary protein supplement, capable of enhancing humoral immune responses to a range of heterologous antigens.

Adjuvants, Immunologic↗

PubMed2003

Development and numerical validation of a finite element model of the muscle standardized femur.

The human femur is one of the parts of the musculo-skeletal system most frequently analysed by means of the finite element (FE) method. Most FE studies of the human femur are based on computed tomography data sets of a particular femur. Since the geometry of the chosen sample anatomy influences the computed results, direct comparison across various models is often difficult or impossible. The aim of the present work was to develop and validate a novel three-dimensional FE model of the human femur based on the muscle standardized femur (MuscleSF) geometry. In the new MuscleSF FE model, the femoral attachment of each muscle was meshed separately on the external bone surface. The model was tested under simple load configurations and the results showed good agreement with the converged solution of a former study. In the future, using the validated MuscleSF FE model for numerical studies of the human femur will provide the following benefits: (a) the numerical accuracy of the model is known; (b) muscle attachment areas are incorporated in the model, therefore physiological loading conditions can be easily defined; (c) analyses of the femur under physiological load cases will be replicable; (d) results based on different load configurations could be compared across various studies.

Compressive Strength↗

PubMed2003

Strain distribution within the human femur due to physiological and simplified loading: finite element analysis using the muscle standardized femur model.

The aim of the current work was to study the effect of simplified loading on strain distribution within the intact femur using the Muscle Standardized Femur finite element model and to investigate whether the interaction between the intact human femur and the muscles which are attached to the bone surface could accurately be represented by concentrated forces, applied through the centroids of their attachment areas. An instant at 10 per cent of the gait cycle during level walking was selected as the reference physiological load case; nine load cases were analysed. Comparison of the calculated results for the physiological load case with muscle forces uniformly distributed over their attachment areas showed good agreement with in vivo measurements of strain values and femoral head displacement in humans. Simplified load cases generated unrealistic displacement results and high strain magnitudes, exceeding the physiological range. It was found that when muscles with large attachment areas are included in the model and the muscle forces are simplified, stress and strain distributions will be affected not only on the external bone surface in the vicinity of the load application node, but also on the internal surface of the cortical bone. However, applying muscle forces as concentrated loads at the centroids of the attachment areas can serve as first indicators of the physiological stress and strain levels, if results from nodes and elements in the vicinity of the load application nodes are discarded. Omitting muscle forces or fixing the femur in mid-shaft leads to large unphysiological strain values.

Compressive Strength↗

PubMed2002

The effect of anteversion on femoral component stability assessed by radiostereometric analysis.

Internal rotation of a femoral stem within the femur, with posterior migration of the femoral head (PHM) relative to the femur, is an important mode of failure. The relationship between anteversion and rotational stability for the Exeter (Howmedica International Ltd, London, UK) and Charnley Elite (DePuy International Ltd, Leeds, UK) stems was investigated using radiostereometric analysis (RSA). For the Elite, there was a significant (P=.01) correlation between anteversion and PHM, whereas for the Exeter, there was no significant correlation (P=.6). Increasing anteversion of the Elite was associated with decreasing PHM and increased stability. Of stems, 20% of the Elite and none of the Exeter were classified as having reduced rotational stability because their PHM was >2 SDs from the mean. All reduced rotational stability implants had anteversion substantially <20 degrees. Polished collarless tapered stems such as the Exeter seem to have enhanced rotational stability. For conventional stems, increasing anteversion increases stability. It is recommended that these stems are anteverted 20 degrees.

Hip Prosthesis↗

PubMed2001

New methodologies for the preparation of porphodimethenes and their conversion to trans-porphyrins with functionalized naphthyl spacers.

The MacDonald [2 + 2]-type condensation of readily available 5-aryl-substituted dipyrromethanes with acenaphthenequinone leads to the trans-syn- and anti-porphodimethenes, which in turn can be converted to the alpha,alpha- and alpha,beta-porphyrin atropisomers, respectively. Treatment of the metalated or unmetalated porphodimethenes with KOH or NaOMe in THF followed by protonation with HCl results in a ring opening of the acenaphthenone and formation of the trans-8-carboxynaphthylporphyrins or their esters (NaOMe) after oxidation. Alternatively, the porphyrin formation can be accomplished by reaction of the porphodimethenes with acids in the presence of water or methanol. Reaction with NaBH(4) in a THF--methanol mixture yields the corresponding dialcohols in nearly quantitative yields. Sixteen different building blocks were prepared in order to evaluate the generality of this new synthetic approach, with Ar = 2,4,6-Me(3)C(6)H(2); 2,6-Cl(2)C(6)H(3); 2,6-F(2)C(6)H(3); 3,4-tBu(2)C(6)H(3); 3,4,5-(MeO)(3)C(6)H(2); 4-BrC(6)H(4); 4-MeC(6)H(4); and 4-MeOOCC(6)H(4) at the meso positions. The synthesized porphodimethenes and porphyrins have been fully characterized, and the X-ray structure analyses of three representative derivatives are presented.

Journal Article↗

PubMed2001

In vitro adherence properties of Lactobacillus rhamnosus DR20 and Bifidobacterium lactis DR10 strains and their antagonistic activity against an enterotoxigenic Escherichia coli.

Adhesion and colonisation properties of three probiotic strains namely, Lactobacillus rhamnosus DR20, L. acidophilus HN017, and Bifidobacterium lactis DR10, were determined in vitro using the differentiated human intestinal cell-lines including HT-29, Caco-2, and HT29-MTX, and compared with properties of L. acidophilus LA-1 and L. rhamnosus GG (two commercial probiotic strains). Two independent methods were employed to quantitate the "adhesiveness" of each strain. In the first method, the bacteria adhered to human cells were detected by Gram staining and counted in different fields under a microscope. Bacteria were also radio-labelled and extent of adhesion determined by scintillation counting. All three strains showed strong adhesion with the human intestinal cell lines in vitro. Adhesion indices of the three strains to two cell lines, i.e. HT-29, and Caco-2 varied between 99 +/- 17 and 219 +/- 36. With mucus-secreting cell-line HT29-MTX, the adhesion indices of all the strains were 2-3 times higher. The adhesion indices of L. acidophilus LA-1 and L. rhamnosus GG were comparable to the other three probiotic strains. We also investigated the inhibitory effect of adhering strains against the intestinal cell monolayer colonization by a known enterotoxigenic strain of Escherichia coli (strain O157:H7). Pre-treatment of E. coli O157:H7 with 2.5-fold concentrated cell-free culture supernatants from L. acidophilus HN017, L. rhamnosus DR20 and B. lactis DR10 reduced the culturable E. coli numbers on TSB plates and also reduced the invasiveness and cell association characteristics of this toxic strain. The inhibitory molecules secreted into the spent media by these strains were partially affected by treatments with lactate dehydrogenase, trypsin and proteinase K suggesting that overall inhibition may be due to a synergistic action of lactic acid and proteinaceous substances.

Bacterial Adhesion↗

PubMed2001

The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition.

Phosphinothricin is a potent inhibitor of the enzyme glutamine synthetase (GS). The resolution of the native structure of GS from Salmonella typhimurium has been extended to 2.5 A resolution, and the improved model is used to determine the structure of phosphinothricin complexed to GS by difference Fourier methods. The structure suggests a noncovalent, dead-end mechanism of inhibition. Phosphinothricin occupies the glutamate substrate pocket and stabilizes the Glu327 flap in a position which blocks the glutamate entrance to the active site, trapping the inhibitor on the enzyme. One oxygen of the phosphinyl group of phosphinothricin appears to be protonated, because of its proximity to the carboxylate group of Glu327. The other phosphinyl oxygen protrudes into the negatively charged binding pocket for the substrate ammonium, disrupting that pocket. The distribution of charges in the glutamate binding pocket is complementary to those of phosphinothricin. The presence of a second ammonium binding site within the active site is confirmed by its analogue thallous ion, marking the ammonium site and its protein ligands. The inhibition of GS by methionine sulfoximine can be explained by the same mechanism. These models of inhibited GS further illuminate its catalytic mechanism.

Aminobutyrates↗

PubMed2001

Potential probiotic lactic acid bacteria Lactobacillus rhamnosus (HN001), Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019) do not degrade gastric mucin in vitro.

The mucus layer (mucin) coating the surface of the gastrointestinal tract (GIT) plays an important role in the mucosal barrier system. Any damage or disturbance of this mucin layer will compromise the host's mucosal defence function. In the present study, the ability of three potential probiotic lactic acid bacteria (LAB) strains (Lactobacillus rhamnosus HN001, Lactobacillus acidophilus HN017, Bifidobacterium lactis HN019) to degrade mucin in vitro was evaluated, in order to assess their potential pathogenicity and local toxicity. The LAB strains were incubated in medium containing hog gastric mucin (HGM, 0.3%) at 37 degrees C for 48 h, following which any decrease in carbohydrate and protein concentration in the ethanol-precipitated portion of the culture medium was determined, using phenol-sulphuric acid and bicinchonic acid (BCA) protein assays, respectively. The change in molecular weight of mucin glycoproteins, following incubation with the test strains, was monitored by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). In order to expose any ability of the test strains to degrade mucin visually and more directly, the test strains were also cultured on agarose containing 0.3% HGM and incubated anaerobically for 72 h at 37 degrees C. No significant change in the carbohydrate or protein concentration in mucin substrates was found following incubation with the test strains. No mucin fragments were derived from the mucin suspension incubated with test strains, and no mucinolysis zone was identified on agarose. These results demonstrate that the potential probiotic LAB strains tested here were unable to degrade gastrointestinal mucin in vitro, which suggests that these novel probiotic candidates are likely to be non-invasive and non-toxic at the mucosal interface.

Anaerobiosis↗

PubMed2001

Protection against translocating Salmonella typhimurium infection in mice by feeding the immuno-enhancing probiotic Lactobacillus rhamnosus strain HN001.

The probiotic lactic acid bacterium Lactobacillus rhamnosus (strain HN001) is known to stimulate enhanced innate and acquired immune responses in mice. following oral delivery. Here, the ability of HN001 to confer immune enhancement and protection against an oral challenge of Salmonella tYphimurium was investigated. HN001-fed and non-probiotic-fed control BALB/c mice were challenged with either a single dose of S. typhimurium (ATCC strain 1772), or with five repeated daily doses of the pathogen; post-challenge clinical, behavioural, bacteriological and immunological parameters were assessed. Mice began to show ostensible signs of infection 3-4 days following the initiation of Salmonella challenge, and the first mortalities were observed after 6 days. Following single-dose Salmonella challenge, HN001-fed mice maintained a higher mean pre-mortality general health score than control mice; retained significantly greater food and water intake and weight gain, produced higher titres of serum and intestinal tract anti-Salmonella antibodies, and showed greater overall survival of infection (27/30 mice surviving at 21 days post-challenge, compared to 2/29 in the control group). Following repeated-dose Salmonella challenge, HN001-fed mice had significantly lower mean pathogen burdens in visceral organs (spleen, liver) compared to controls, and additionally, blood and peritoneal leucocytes obtained from HN001-fed mice exhibited significantly higher ex vivo phagocytic capacity compared to control-mice. This study affirms that Lb. rhamnosus strain HN001 displays immuno-enhancing properties in S. typhimurium-infected mice, and demonstrates that oral delivery of this probiotic can promote increased protection against a highly virulent enteric bacterial pathogen.

Animals↗