Biomedical subjects

M Sims

Publications and source records attributed to M Sims.

At least 19 recordsLinked to original sources

PubMed2006

Studies of the SIM1 gene in relation to human obesity and obesity-related traits.

OBJECTIVE: The single-minded 1 (SIM1) is a basic helix-loop-helix transcription factor, which plays a critical role in the development of the paraventricular nucleus (PVN) of the hypothalamus. SIM1-deficient mice have a hypocellular PVN and are severely obese with increased food intake. DESIGN: We examined whether variants in the SIM1 gene might be associated with severe early-onset obesity in humans. Two hundred and seventy-seven subjects with hyperphagia and severe, early-onset obesity were screened. Association studies with common single-nucleotide polymorphisms (SNPs) in the SIM1 gene were performed in two population-based cohorts. RESULTS: One novel missense mutation, I128T, was found in one obese subject and not in 192 controls. However, the variant did not co-segregate with obesity in the family. Four SNPs, IVS4+83GA, P352T, A371V and T653T, were also identified. The two common SNPs, P352T and A371V, which are in complete linkage disequilibrium, were genotyped in 981 subjects from a population-based cohort, the Ely Study. An allele frequency of 0.13 was observed. Male subjects carrying the P352T/A371V haplotype were found to have a slightly higher body mass index (BMI; P=0.038). Female subjects homozygous for the haplotype gained more weight over a period of 4.5 and 10 years (P=0.003 and P=0.02, respectively). The association studies were repeated in another population-based cohort, the European Prospective Investigation into Cancer and Nutrition (EPIC) - Norfolk Study with 4869 subjects successfully genotyped. Male subjects homozygous for the P352T/A371V haplotype had slightly higher BMI (P=0.04). CONCLUSION: Mutations in SIM1 are not commonly found in humans with severe early-onset obesity. The relationship between the common variants in SIM1 with BMI and body weight gain deserves further exploration in other populations.

Basic Helix-Loop-Helix Proteins↗

PubMed2006

Children's cortisol levels and quality of child care provision.

BACKGROUND: Cortisol levels are increasingly being used as an indicator of stress levels. Research suggests that children who attend child care demonstrate higher cortisol levels than children in their homes, suggesting that child care acts as a risk factor for poor child outcomes. However, it is also suggested that quality influences outcomes. METHODS: Cortisol levels were measured through samples of saliva taken from children (3-5 years of age) attending long-day care centres in Perth, Western Australia. Quality of the programme was measured using industry national quality assurance indicators designed for child care centres. The analysis employed a 2 (time of collection: average am cortisol, average pm cortisol) by 3 (centre quality: high, satisfactory, unsatisfactory) split plot ANOVA with repeated measures on the time factor. RESULTS: Cortisol levels of children attending high-quality programmes demonstrated a decline across the child care day. Levels in children attending unsatisfactory programmes demonstrated an increase across the day. CONCLUSIONS: Although we do not yet know how high, and for how long, cortisol levels need to be elevated for risk of undesirable outcomes to increase, this research signals the importance of emphasizing the need for high-quality care for young children.

Analysis of Variance↗

PubMed2004

Evidence from Opportunity's Microscopic Imager for water on Meridiani Planum.

The Microscopic Imager on the Opportunity rover analyzed textures of soils and rocks at Meridiani Planum at a scale of 31 micrometers per pixel. The uppermost millimeter of some soils is weakly cemented, whereas other soils show little evidence of cohesion. Rock outcrops are laminated on a millimeter scale; image mosaics of cross-stratification suggest that some sediments were deposited by flowing water. Vugs in some outcrop faces are probably molds formed by dissolution of relatively soluble minerals during diagenesis. Microscopic images support the hypothesis that hematite-rich spherules observed in outcrops and soils also formed diagenetically as concretions.

Extraterrestrial Environment↗

PubMed2004

The Opportunity Rover's Athena science investigation at Meridiani Planum, Mars.

The Mars Exploration Rover Opportunity has investigated the landing site in Eagle crater and the nearby plains within Meridiani Planum. The soils consist of fine-grained basaltic sand and a surface lag of hematite-rich spherules, spherule fragments, and other granules. Wind ripples are common. Underlying the thin soil layer, and exposed within small impact craters and troughs, are flat-lying sedimentary rocks. These rocks are finely laminated, are rich in sulfur, and contain abundant sulfate salts. Small-scale cross-lamination in some locations provides evidence for deposition in flowing liquid water. We interpret the rocks to be a mixture of chemical and siliciclastic sediments formed by episodic inundation by shallow surface water, followed by evaporation, exposure, and desiccation. Hematite-rich spherules are embedded in the rock and eroding from them. We interpret these spherules to be concretions formed by postdepositional diagenesis, again involving liquid water.

Atmosphere↗

PubMed2004

Textures of the soils and rocks at Gusev Crater from Spirit's Microscopic Imager.

The Microscopic Imager on the Spirit rover analyzed the textures of the soil and rocks at Gusev crater on Mars at a resolution of 100 micrometers. Weakly bound agglomerates of dust are present in the soil near the Columbia Memorial Station. Some of the brushed or abraded rock surfaces show igneous textures and evidence for alteration rinds, coatings, and veins consistent with secondary mineralization. The rock textures are consistent with a volcanic origin and subsequent alteration and/or weathering by impact events, wind, and possibly water.

Extraterrestrial Environment↗

PubMed2004

The Spirit Rover's Athena science investigation at Gusev Crater, Mars.

The Mars Exploration Rover Spirit and its Athena science payload have been used to investigate a landing site in Gusev crater. Gusev is hypothesized to be the site of a former lake, but no clear evidence for lacustrine sedimentation has been found to date. Instead, the dominant lithology is basalt, and the dominant geologic processes are impact events and eolian transport. Many rocks exhibit coatings and other characteristics that may be evidence for minor aqueous alteration. Any lacustrine sediments that may exist at this location within Gusev apparently have been buried by lavas that have undergone subsequent impact disruption.

Atmosphere↗

PubMed2004

Evaluation of a new quantitative technique to assess the number and extent of preferred retinal loci in macular disease.

Patients with scotomas due to macular disease may use more than one preferred retinal locus (PRL) for fixation. We have developed and evaluated an objective, quantitative technique to determine the number of PRLs used during an episode of fixation and the extent of each locus. In five of eight adults with macular disease our techniques consistently indicated the presence of multiple PRLs. Patients with multiple PRLs were more likely to have suffered recent vision loss in the tested eye. Our technique describes fixation more fully than the traditional method of calculating a single bivariate contour ellipse area.

Adult↗

PubMed2001

Light microscopic and scanning electron microscopic retrieval analyses of implanted biomaterials retrieved from humans and experimental animals.

This paper reports analysis obtained from 200 implant cases retrieved from humans and submitted to the American Academy of Implant Dentistry Research Foundation, Medical College of Georgia implant retrieval center. The samples that were not decalcified were embedded in polymethylmethacrylate and examined with scanning electron microscopy and routine light, polarized, or Nomarski microscopy. Cases included both orthopedic and dental implants, as well as entire mandibles and portions of maxillae obtained at autopsy. A significant number of submitted implants had substantial amounts of adhered bone, which permitted evaluation of human bone remodeling to osseointegrated implants. These implants failed because of implant fracture. As was observed with animal studies, healthy bone supported these implants, with the bone containing an interdigitating canaliculi network that provided communication between interfacial osteocytes and osteocytes deeper within the remodeled osteonal and trabecular bone. Early dental implants containing a coating of beads showed a connective tissue interface, which corresponded to the bead surface of specific orthopedic implants that underwent some degree of micromovement. This is in contrast with the excellent response reported for successful contemporary beaded implants. Significant numbers of osseointegrated fractured hydroxyapatite (HA)-coated dental implants demonstrated the adequate serviceability of these implants before biomaterial fracture. In contrast, the HA coating was dissociated from retrieved orthopedic implants, leading to extensive cup loosening and case failure. This study, therefore, underscores the need for evaluation of failed human dental and orthopedic implants. Correlations can be drawn between human retrieval and experimental animal studies.

Aluminum Oxide↗

PubMed2000

Molecular cloning and characterization of two novel retinoic acid-inducible orphan G-protein-coupled receptors (GPRC5B and GPRC5C).

Using homology searching of public databases with a metabotropic glutamate receptor sequence from Caenorhabditis elegans, two novel protein sequences (named RAIG-2 (HGMW-approved symbol GPRC5B) and RAIG-3 (HGMW-approved symbol GPRC5C) were identified containing seven putative transmembrane domains characteristic of G-protein-coupled receptors (GPCRs). RAIG-2 and RAIG-3 encode open reading frames of 403 and 442 amino acid polypeptides, respectively, and show 58% similarity to the recently identified retinoic acid-inducible gene-1 (RAIG-1, HGMW-approved symbol RAI3). Analysis of the three protein sequences places them within the type 3 GPCR family, which includes metabotropic glutamate receptors, GABA(B) receptors, calcium-sensing receptors, and pheromone receptors. However, in contrast to other type 3 GPCRs, RAIG-1, RAIG-2, and RAIG-3 have only short N-terminal domains. RAIG-2 and RAIG-3 cDNA sequences were cloned into the mammalian expression vector pcDNA3 with c-myc or HA epitope tags inserted at their N-termini, respectively. Transient transfection experiments in HEK239T cells using these constructs demonstrated RAIG-2 and RAIG-3 expression at the cell surface. Distribution profiles of mRNA expression obtained by semiquantitative Taq-Man PCR analysis showed RAIG-2 to be predominantly expressed in human brain areas and RAIG-3 to be predominantly expressed in peripheral tissues. In addition, expression of RAIG-2 and RAIG-3 mRNA was increased following treatment with all-trans-retinoic acid in a manner similar to that previously described for RAIG-1. Finally, RAIG-2 was mapped to chromosome 16p12 (D16S405-D16S3045) and RAIG-3 to chromosome 17q25 (D17S1352-D17S785). These results suggest that RAIG-1, RAIG-2, and RAIG-3 represent a novel family of retinoic acid-inducible receptors, most closely related to the type 3 GPCR subfamily, and provide further evidence for a linkage between retinoic acid and G-protein-coupled receptor signal transduction pathways.

Amino Acid Sequence↗

PubMed2000

Intraocular bacterial contamination during sutureless, small incision, single-port phacoemulsification.

PURPOSE: To evaluate the incidence of anterior chamber bacterial contamination during no-stitch, 1-handed, small incision phacoemulsification. SETTING: Little Company of Mary Hospital, Evergreen Park, Illinois, USA. METHODS: This study comprised 53 eyes of 46 patients. Topical gentamicin sulfate was administered 1 hour preoperatively. After povidone-iodine cleansing solution and povidone-iodine paint (5% and 10%) were applied, the eyes were draped in a sterile manner. Aqueous fluid was aspirated upon entering the anterior chamber and at the end of surgery; the specimens were cultured for up to 14 days. All eyes had no-stitch, 1-handed, small incision phacoemulsification with implantation of a foldable acrylic posterior chamber intraocular lens through a 3.5 mm scleral tunnel incision. RESULTS: Three specimens (5.7%) aspirated on entry into the anterior chamber were positive for microorganisms. Of the cultures obtained at the end of surgery, 4 (7.5%) were positive for microorganisms. All posterior lens capsules were intact. The following organisms were cultured at the end of phacoemulsification: alpha-streptococci, micrococci, saprophytic mold, alpha-viridans streptococci, coagulase-negative Staphylococcus species, and anaerobic positive cocci. No eye developed endophthalmitis. CONCLUSIONS: The incidence of anterior chamber bacterial contamination was low. Bacterial contamination of the anterior chamber occurred at the beginning and toward the end of phacoemulsification. Staphylococcus species was the most common organism in the beginning, while Streptococcus species was the most common at the end. Saprophytic mold was present only at the end. No eye developed endophthalmitis.

Aged↗

PubMed2000

Prebiotic methylation and the evolution of methyl transfer reactions in living cells.

An hypothesis is presented for the prebiotic origin of methyl groups and the evolution of methyl transfer reactions in living cells. This hypothesis, described in terms of prebiotic and early biotic chemical evolution, is based on experimental observations in our lab and in those of others, and on the mechanisms of enzymatic methyl transfer reactions that occur in living cells. Of particular interest is our demonstration of the reductive methylation of ethanolamine and glycine in aqueous solution by excess formaldehyde. These reactions, involving prebiotic compounds and conditions, are mechanistically analogous to the de novo origin of methyl groups in modern cells by reduction of methylene tetrahydrofolate. Furthermore, modern cellular methyl transfers from S-adenosylmethionine to amine nitrogen may involve formaldehyde as an intermediate and subsequent reductive methylation, analogous to the prebiotic chemistry observed herein.

Betaine↗

PubMed2000

Identification of a novel kidney-specific gene downregulated in acute ischemic renal failure.

To gain further insights into the molecular mechanisms involved in acute renal failure, we have isolated a new gene from rat and human, named KSP32 (kidney-specific protein with a molecular mass of 32 kDa). KSP32 encodes a novel gene that shows little homology to other mammalian proteins. It, however, shares extensive homology with several proteins found in the nematode Caenorhabditis elegans and plants. The expression of KSP32 mRNA is highly restricted to kidney. In situ hybidization analysis revealed that the expression of KSP32 mRNA was prominent in the boundary of kidney cortex and outer medulla, exhibiting a raylike formation extending from the medulla into the cortex. Finally, KSP32 mRNA was dramatically downregulated in rat following induction of acute ischemic renal failure. Rapid loss of KSP32 mRNA expression was observed beginning at approximately 5 h following renal injury and mRNA levels remained depressed for at least 96 h. Both KSP32 mRNA levels as well as renal function recovered 14 days after injury. Administration of an endothelin receptor antagonist (SB-209670), known to restore renal function, significantly increased KSP32 expression.

Acute Kidney Injury↗

PubMed1999

Limb reconstruction after high energy trauma.

Limb reconstruction techniques rely on stable external fixation to provide early limb function after major long bone injury. Bone may be generated by callus distraction techniques and internal techniques of moving bone segments used to fill bone defects. Soft tissue defects may be treated by acute shortening, although skin defects will also close spontaneously during bone transport as the leading edge of bone is covered with granulation tissue. External fixation is also used to cross joints permitting rest and repair of the joint. Hinges placed within the bars of the fixation frame may be used to correct deformities in the bone and soft tissue contractures using closed distraction techniques. These techniques are appropriate to metaphyseal fractures and diaphyseal fractures with bone loss. A major advantage is the lack of donor site morbidity, associated with skin flaps and large bone grafts. Acceptance of these techniques is growing whilst the methodology continues to improve. In more complicated cases, specialist training and dedicated hospital units with multidisciplinary support is desirable.

External Fixators↗

PubMed1998

An oligo-screening strategy to fill gaps found during shotgun sequencing projects.

During the course of projects to sequence human and nematode cosmids we encountered great difficulties generating contiguous sequence in regions with repetitive DNA (Alu repeats in humans and tandem or inverted repeats in the nematode). We have developed a simple and efficient strategy to fill gaps. By screening M13, plasmid or phagemid libraries with oligonucleotides flanking the gap, clones are identified that contiguate the cosmid sequence. Our method has been integrated into the GAP4 sequence assembly program. The strategy reduces both time and costs in large scale sequencing projects.

Animals↗

PubMed1997

Antibody selection against CD52 produces a paroxysmal nocturnal haemoglobinuria phenotype in human lymphocytes by a novel mechanism.

The CD52 antigen is a lymphocyte glycoprotein with an extremely short polypeptide backbone and a single N-linked glycan, and it is attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. Treatment of rheumatoid arthritis patients with CAMPATH-1H, a humanized monoclonal antibody against CD52, resulted, in a small number of cases, in the appearance and persistence of CD52-negative T cells. Similarly, CD52-negative B cells emerged following in vitro treatment of a CD52-positive human B cell line with CAMPATH-1H. Both the B and T CD52-negative cells were also found to be defective in surface expression of other GPI-anchored proteins. Biochemical analysis revealed a severe defect in the synthesis of a mature GPI precursor in both the B and T cell lines. Therefore the phenotype of these CD52-negative B and T cells closely resembles that of lymphocytes from patients with paroxysmal nocturnal haemoglobinuria (PNH), in which the first step of the GPI-biosynthetic pathway, i.e. synthesis of GlcNAc-phosphatidylinositol, is blocked. In all cases studied to date, this defect maps to a mutation of the phosphatidylinositolglycan class A (PIG-A) structural gene. We therefore amplified the PIG-A gene from both the GPI-negative B and T cells by PCR and determined the nucleotide sequence. No differences from the wild-type sequence were detected; therefore a classical PNH mutation cannot be responsible for the GPI-biosynthesis defect in these cell lines. Significantly, the GPI-negative phenotype of the B cells was reversible upon separation of the positive and negative cells, resulting in a redistribution to a mixed population with either CD52-positive or -negative cells, whereas populations of 100% CD52-negative T cells were stably maintained during culture. Therefore, whereas the GPI-biosynthesis deficiency in the T cell lines may be due to a mutation in another gene required by the GPI-biosynthetic pathway, the reversible nature of this block in the B cell lines suggests a less direct cause, possibly an alteration in a regulatory factor. Overall, these data demonstrate that the PNH phenotype can be generated without a mutation in the PIG-A structural gene, and thereby identify a novel mechanism for the development of GPI deficiency.

Alemtuzumab↗

PubMed1997

Coinfection with Giardia lamblia and Enterocytozoon bieneusi in a patient with acquired immunodeficiency syndrome and chronic diarrhea.

Diarrhea is an important clinical problem in immunosuppressed patients with acquired immunodeficiency syndrome (AIDS). There are numerous classical as well as emerging enteric pathogens that can produce diarrhea; however, these agents can be missed when only one method, such as microbiological examination of stool, is used for diagnosis. The endoscopic biopsy is a sensitive method for diagnosis of many viral, fungal, and parasitic infections of the gastrointestinal tract. Although only one agent is often identified in mucosal biopsies from these immunosuppressed patients, coinfection with multiple microbial agents is being increasingly recognized. Giardia infection is not as prevalent as other pathogens in patients with AIDS, but it remains an important diarrheal agent that is potentially curable. However, there have been only rare reports of coinfections with giardiasis and other infectious agents. This report describes a patient with AIDS and chronic diarrhea who had repeated negative stool examinations for ova and parasites. Light and electron microscopic examination of subsequent endoscopically obtained small intestinal biopsies revealed coinfection with two parasites, Enterocytozoon bieneusi and Giardia lamblia. Following treatment with metronidazole for giardiasis, the diarrhea persisted, but was less severe. This report also describes the diagnostic features of Giardia and Enterocytozoon infections in biopsy tissues and emphasizes the importance of identifying enteric coinfections in patients with AIDS to ensure timely and specific modes of therapy.

AIDS-Related Opportunistic Infections↗

PubMed1996

Solution structure of a biologically active cyclic LDV peptide analogue containing a type II' beta-turn mimetic.

The solution structure of cyclo-[Gly-Leu-Asp-Val-BTD] (BTD = beta-turn dipeptide) has been determined by two-dimensional 1H-NMR (nuclear magnetic resonance) spectroscopy and systematic conformational searching combined with molecular dynamics studies. The structure contains two hydrogen bonds between the Gly and Val residues, and a type I beta-turn with Leu and Asp at the (i + 1) and (i + 2) positions of the turn. The cyclic compound shows activity in a scintillation proximity assay (SPA) for the inhibition of the interaction between the integrin alpha 4 beta 1 and vascular cell adhesion molecule-1 (VCAM-I). The structure-activity relationship of the LDV sequence is discussed.

Cloning, Molecular↗

PubMed1996

Protocols for the care of external fixator pin sites.

Pin site care methods used in the UK are based on doctor/nurse preference rather than research. There is a diversity of opinion regarding the best method of pin site care, and no standardised classification of pin site problems. There is a need for further research, either a multi-centre trial or in units with a high volume of work.

Bandages↗