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Biomedical subjects

M Allen

Publications and source records attributed to M Allen.

At least 55 records · Page 3Linked to original sources

The effects of particulate polyethylene at a weight-bearing bone-implant interface. A study in rats.

In ten male rats we inserted ceramic 'drawing-pin' implants in weight-bearing positions within the right proximal tibia. Two animals were killed 6 weeks after surgery and two more 14 weeks after surgery. The remaining six received intra-articular injections of either high-density polyethylene (4 rats) or saline (2 rats) at 8, 10 and 12 weeks after surgery. These animals were killed two weeks after the last injection. Histological examination of the bone-implant interface in the control animals showed appositional bone growth around the implant at both 6 and 14 weeks. Polyethylene, but not saline, caused a chronic inflammatory response with numerous foreign-body giant cells in periprosthetic tissues. Our model of a stable, weight-bearing bone-implant interface provides a simple and reliable system in which to study in vivo the effects of particulate materials used in orthopaedic surgery.

Animals

Evolutionary importance for the membrane enhancement of the production of vitamin D3 in the skin of poikilothermic animals.

The photoproduction of vitamin D in the skin was essential for the evolutionary development of terrestrial vertebrates. During exposure to sunlight, previtamin D3 formed in the skin is isomerized to vitamin D3 (calciol) by a temperature-dependent process. Since early land vertebrates were poikilothermic, the relatively slow conversion of previtamin D3 to vitamin D3 at ambient temperature put them at serious risk for developing vitamin D deficiency, thus leading to a poorly mineralized skeleton that could have ultimately halted further evolutionary development of vertebrates on land. We evaluated the rate of isomerization of previtamin D3 to vitamin D3 in the skin of iguanas and found the isomerization rate was enhanced by 1100% and 1700% at 25 degrees C and 5 degrees C, respectively. It is likely that the membrane entrapment of previtamin D3 in its s-cis,s-cis conformation is responsible for the markedly enhanced conversion of previtamin D3 to vitamin D3. The membrane-enhanced production of vitamin D3 ensures the critical supply of vitamin D3 to poikilothermic animals such as iguanas.

Animals

Sensory modulation of auditory stimuli in children with autism and receptive developmental language disorder: event-related brain potential evidence.

Three groups of age- and PIQ-matched children (Autism, Receptive Developmental Language Disorder, and normal controls) participated in two event-related brain potential (ERP) experiments. Each of these experiments was aimed at evaluating whether either of the two clinical groups of children demonstrated abnormalities in two auditory ERP components, N1 and P2, which are known to be dependent on stimulus characteristics (frequency, intensity, and probability), and believed to be generated within primary and secondary cortex. Results of Experiment 1 provide partial support for the idea that both clinical groups failed to fully process changes in stimulus intensity as indexed by the N1 component. Results are discussed in reference to potential abnormalities in serotonergic regulation of auditory cortex.

Adolescent

Formoguanamine-induced inhibition of deprivation myopia in chick is accompanied by choroidal thinning while retinal function is retained.

Twenty hatchling chickens were injected intravitreally every 4 days from day 2 to day 16 with dimethyl sulphoxide (DS) in one eye and DS or formoguanamine dissolved in DS (FG.DS) with or without occlusion in the other (FG.DS.MD, DS.MD, FG.DS). At day 16, the FG.DS.MD eyes failed to show the high refractive myopia and showed less axial elongation than that developed by the DS.MD eyes. Electroretinograms indicated that at the dosage used, FG.DS does not eliminate phototransduction. Light microscopy showed choroidal and retinal thinning in DS.MD and FG.DS.MD eyes but less than in FG.DS eyes, suggesting that change in choroidal thickness is unlikely to be the primary cause of form deprivation myopia.

Animals

The association of thirst, sodium appetite and vasopressin release with c-fos expression in the forebrain of the rat after intracerebroventricular injection of angiotensin II, angiotensin-(1-7) or carbachol.

The effect intracerebroventricular injections of angiotensin II (0.1 nm), angiotensin-(1-7) (1 or 100 nm) and carbachol (500 ng) on c-fos expression was examined in the forebrain of Lister hooded rats. Intense staining of the c-Fos protein was found in the median preoptic nucleus, organum vasculosum of the lamina terminalis, subfornical organ, paraventricular nucleus and supraoptic nucleus after angiotensin II and carbachol Angiotensin II caused significantly more c-fos expression in the ventral median preoptic nucleus and organum vasculosum of the lamina terminalis than carbachol, whereas in the paraventricular and supraoptic nuclei this was reversed, with carbachol having a greater effect on c-fos expression in these areas. Angiotensin-(1-7), however, only induced c-Fos protein in the organum vasculosum of the lamina terminalis and median preoptic nucleus with the number and the intensity of staining of the nuclei significantly less in both areas than after angiotensin II or carbachol. Separate groups of Lister rats were given i.c.v. injections of the same substances at the same doses, but excluding the lower dose of angiotensin-(1-7), and the intakes of water and 1.8% NaCl over 60 min were measured. Angiotensin II stimulated intakes of both water and NaCl. The effect on water intake was almost immediate (<1 min), whereas NaCl intake did not usually start until at least 5 min after injection. Over 60 min, water (12.4 +/- 1.0 ml) and NaCl (4.2 +/- 0.9 ml) intakes were significantly greater than water (1.1 +/- 0.2 ml) and NaCl (0.6 +/- 0.5 ml) intakes of the controls. Carbachol caused less drinking than angiotensin II, the water intake over 60 min being significantly less (4.8 +/- 0.7 ml) and the latency of response greater (>5 min). Carbachol, unlike angiotensin II, had little effect on NaCl intake (0.7 +/- 0.4 ml). Angiotensin-(1-7) had no effect on water (1.1 +/- 0.3 ml) or NaCl (0.3 +/- 0.3 ml) intakes. The plasma levels of vasopressin were measured after i.c.v. injection of the same three substances in the same doses, again excluding the lower dose of angiotensin-(1-7), in further groups of rats. Angiotensin II and carbachol caused an approximate five-fold increase in plasma vasopressin levels compared to cerebrospinal fluid-injected rats, but angiotensin-(1-7) had no effect on vasopressin release. Therefore, three compounds with widely differing effects on thirst, sodium appetite and vasopressin release induce distinctive patterns of c-fos protein expression in the forebrain. By combining experimental approaches in this way it is possible to determine areas of the brain which are involved in certain behavioural and endocrine responses.

Angiotensin I

The fate of the osteotomized free radial forearm osteocutaneous flap in mandible reconstruction.

The radial forearm osteocutaneous free flap has become a standard method of mandible reconstruction. In order to improve the contour of the reconstructed jaw in large resections, especially the anterior defect, the radial forearm bone graft needs to be osteotomized. The bone graft is nourished by small branches of the radial artery via the fascial connections between the skin flap and bone. The effect of the osteotomy, fixation devices, and the angulation of the bone segment on bone viability and eventual bone healing is not known. Forty-two radial forearm osteocutaneous flaps were used for composite mandible reconstruction. In 25 patients, the bone graft required osteotomy to achieve contour, of which 16 required single osteotomy and nine required double osteotomy. In a remaining 17 cases, no osteotomy was performed. Only those patients who had at least a 1-year follow-up were included in this study. The proportion of patients who achieved bone union was similar for both groups (i.e. osteotomy vs. nonosteotomy). Performing osteotomies on the segment of the radius in free osteocutaneous transfers is safe, and it allows for more flexibility in reconstruction, to achieve a natural-appearing jaw.

Adult

Pediatrician's communication style: relationship to parent's perceptions and behaviors.

Investigated physician-parent communication styles and the effects of concordance between parent's desired communication styles and the communication style exhibited by physicians. Subjects were 107 parents of children scheduled for an appointment with a pediatrician at a general medical clinic. Parents and physicians completed rating forms indicating the degree to which parents desired each of four communication styles (information giving, interpersonal sensitivity, partnership, and directing one's own treatment). Parents and physicians also rated the degree to which they believed the physician exhibited each of these four styles. Follow-up interviews with parents assessed the level of satisfaction with the visit, perception that parent's concerns had been addressed, and subsequent telephone calls to the physician. Results indicated that physicians underestimated the degree of interaction desired by the parents. Parent desires for particular communication styles were not predicted by characteristics of the parents. Interaction variables predicted parent perceptions and subsequent need for contact with the physician.

Adolescent

Analysis of HLA-class II DQA1, DQB1, DRB1 and DPB1 in Italian multiple sclerosis patients.

We studied the allelic constitution at the HLA class II DQA1, DQB1, DRB1 and DPB1 in 94 Italian multiple sclerosis (MS) patients and 98 controls. No significant increase in the frequency of DR2 alleles was detected among MS patients, as previously observed both in European and some Italian studies. A slight increase was found for the DQA1*0301 and DQB1*0602 alleles in the MS patients. No significant association was found with the glutamine residue at position 34 of the DQ alpha chain, which was noted previously in MS patients from northern Europe.

Alleles

Understanding and using meta-analysis.

Meta-analysis represents a technique with almost limitless potential to improve the practice of persons in the health professions. However, the technique is not without limitations that deserve careful consideration when going over any meta-analytic finding. The essay provides some perspectives on the possible uses of meta-analyses and standards that permit the evaluation of the worth of any particular meta-analysis. As with primary research, the meta-analytic reviewer must make a decision, and the consumer (reader) must evaluate those choices. This article offers an exploration of those choices and some of the potential consequences of those choices.

Data Collection

Altered vascular endothelium integrin expression in psoriasis.

Considerable evidence indicates that microvascular changes observed in psoriasis are a result of vascular proliferation. A critical step in the sequence of events leading to neovascularization involves interactions between endothelial cells and extracellular matrix proteins mediated in part by the integrin family of adhesion molecules. A number of endothelial integrins have been shown to participate in neovascularization, including members of the beta 1, beta 3, and beta 4 subfamilies. To investigate the role of these integrins in psoriasis, specimens of lesional and nonlesional skin were taken from 10 patients with active, untreated plaque disease. Vascular endothelium was labeled with monoclonal antibodies specific for alpha 2, alpha 5, alpha 6, beta 1, av beta 3, and beta 4 integrins. The use of image analysis permitted quantification of immunoperoxidase staining and comparison of endothelial labeling in lesional and nonlesional skin. There was a significant increase in endothelial staining of av beta 3 integrin in lesional compared with nonlesional skin, both in superficial and deep vasculature. In contrast, there was a significant decrease in endothelial beta 4 staining in lesional compared with nonlesional superficial dermal vessels, alpha 2, alpha 5, alpha 6, and beta 1 staining showed no significant difference between the two groups. These results demonstrate an important role of av beta 3 and beta 4 integrins in the microvascular changes of psoriatic lesions.

Adult

Allele-specific HLA-DRB1 amplification of forensic evidence samples with mixed genotypes.

A major problem in analyzing forensic casework samples is the presence of genetic material from more than one individual in the material evidence. For instance, in sexual assault cases the evidence (vaginal swabs) usually contains a majority of vaginal epithelial cells and varying amounts of sperm cells from the perpetrator. Samples with mixed genotypes are also common among other biological evidence materials such as nail scrapes and mixed bloodstains. We have developed an allele-specific amplification system for the highly polymorphic HLA class II DRB1 locus that permits the detection of individual alleles in a sample with mixed genotypes, independent of the initial frequency of the alleles. Using a set of eight allele-specific amplification primers and typing the amplified fragments with sequence-specific probes, most of the 60 DRB1 alleles can be resolved. The method is highly specific and sensitive, with the potential for amplifying 15 copies of a particular allele in a background of 3 x 10(5) copies of other alleles. The method was successfully applied to three forensic cases, where the material evidence consisted of sperm stains on panties, nail scrapes and bloodstains on skin. Thus the DRB1 allele-specific amplification system can be employed for the unambiguous determination of the presence of individual alleles in materials suspected to contain mixed genotypes, even when the alleles of interest constitute only a small fraction of the total DNA.

Alleles

Toxicity of particulate silicon carbide for macrophages, fibroblasts and osteoblast-like cells in vitro.

There is widespread interest in the use of interfacial layers in the preparation of diamond and diamond-like carbon (DLC) coatings. These DLC coatings deposited onto metal substrates with a silicon carbide (SiC) interfacial layer exhibit improved adhesion and show promise as wear-retardant coatings for biomedical implants. Although the DLC coatings show excellent biocompatibility in vitro, they may be susceptible to damage within the biological environment, leading to exposure of the interfacial silicon carbide. We have investigated the effects of two forms of silicon carbide (alpha-SiC and beta-SiC) on macrophages, fibroblasts and bone cells in vitro. Both alpha- and beta-SiC are well-tolerated by cells at concentrations of up to 0.1 mg/ml but cause severe cytotoxicity at a concentration of 1 mg/ml. If SiC is to be used as an interfacial layer on biomedical implants, the quality of the DLC coating must be optimised to minimise the risk of film breakdown.

Adhesiveness

Biphasic effects of intraaccumbens mu-opioid peptide agonist DAMGO on locomotor activities.

The effects of bilateral microinjections of mu-opioid receptor agonist DAMGO (0.00, 0.01, 0.1, or 1.0 microgram/side) were tested in rats for 120 min in activity monitors. The horizontal movement, rearing, and stereotypy times in seconds were measured during 12 consecutive 10-min time blocks. DAMGO (0.01, 0.1, and 1.0 microgram) resulted in biphasic effects, inhibition followed by activation for each of the three measures. These data replicate the behavioral effects of ICV DAMGO except that the duration of the behavioral effects were longer with Acb injections.

Amino Acid Sequence

A comprehensive polymerase chain reaction-oligonucleotide typing system for the HLA class I A locus.

A comprehensive system for genetic typing of the HLA class I A locus is described, based on PCR amplification and typing with nonradioactively labeled SSO probes. Exons 1-3 of the A locus are amplified and typing is performed with a set of 30 nonradioactively labeled oligonucleotide probes. This system resolves 34 of 39 known alleles and 561 (94%) of 595 possible genotypes. Among a sample of 354 individuals from Sweden and China, 97.5% of the genotypes were resolved. Probes were directed preferentially at replacement substitutions in foreign antigen-binding sites, in order to detect not only the known alleles but also new combinations of polymorphic motifs, indicative of previously unrecognized alleles. Three individuals were found with a new combination of polymorphic motifs, suggesting the presence of at least one previously undescribed allele in the populations sampled. This typing system is useful for disease association studies, tissue typing, and in forensic medicine.

Base Sequence

Association of susceptibility to multiple sclerosis in Sweden with HLA class II DRB1 and DQB1 alleles.

The association of MS with HLA class II alleles was studied by PCR-based typing of the DQA1, DQB1, DRB1, and DPB1 loci in 94 Swedish patients with relapses and remissions of the disease. The haplotype DRB1*1501-DQA1*0102-DQB1*0602 was found to be positively associated and three haplotypes were found to be negatively associated with MS. Linkage disequilibrium makes it difficult to assess whether DRB1 or DQB1 plays the primary role in the disease association, while the association with DPB1 and DQA1 appears to be secondary to that of DQB1 and DRB1. Two of the three haplotypes negatively associated with MS carry the DQB1*0301 allele. Also, the negatively associated DRB1*0401-DQA1*0301-DQB1*0301 haplotype differs from those with nonassociated DRB1*0401-DQA1*0301-DQB1*0302 haplotype only at DQB1. These results suggest that DQB1 alleles, as well as some DRB1 alleles, are involved in susceptibility and protection to MS. In searching for sequence motifs in the DR beta chain associated with MS susceptibility, all DRB1 alleles on haplotypes positively associated with MS, including the DRB1*1501, were found to encode a Val at position 86 of the DR beta chain. Also, DRB1 alleles that are negatively associated with MS all encode a Gly at position 86, suggesting that the residue at position 86 may be critical in conferring susceptibility and protection to MS. Finally, when the effect of the DRB1*1501 haplotype was removed there was no support for the hypothesis that MS is associated with a putative DQ-alpha beta heterodimer, encoded for by certain DQA1 and DQB1 alleles.

Alleles

The effects of diamond-like carbon coatings on macrophages, fibroblasts and osteoblast-like cells in vitro.

The elaboration of metallic and polymeric particles from the wear of joint replacement components is widely implicated in the pathogensis of aseptic loosening of these implants. Diamond-like carbon (DLC) coatings show great potential as wear-retardant coatings and may offer a possible solution to this problem. We have studied the effects of DLC coatings on cells derived from the tissues that surround a total joint replacement (macrophages, fibroblasts and osteoblast-like cells). There was no evidence that DLC coatings, deposited on a variety of different substrates, caused cytotoxicity in vitro. Cells grown on the coated substrates exhibited normal cellular growth and morphology. DLC coatings are biocompatible in vitro and should now be tested in animal models to determine their behaviour in vivo.

Animals