Search PubMed⌕ Search

Biomedical subjects

J R Smith

Publications and source records attributed to J R Smith.

At least 37 records · Page 2Linked to original sources
PubMed2004

Phagocytosis of opsonized apoptotic cells: roles for 'old-fashioned' receptors for antibody and complement.

Efficient phagocytic clearance of apoptotic cells is crucial in many biological processes. A bewildering array of phagocyte receptors have been implicated in apoptotic cell clearance, but there is little convincing evidence that they act directly as apoptotic cell receptors. Alternatively, apoptotic cells may become opsonized, whereby naturally occurring soluble factors (opsonins) bind to the cell surface and initiate phagocytosis. Evidence is accumulating that antibodies and complement proteins opsonize apoptotic cells, leading to phagocytosis mediated by well-defined 'old-fashioned' receptors for immunoglobulin-Fc and complement. In this review we summarize the evidence that opsonization is necessary for high capacity clearance of apoptotic cells, which would render putative direct apoptotic cell receptors redundant.

Acute-Phase Proteins↗
PubMed2004

Traumatic partial hypopituitarism in a cat.

Traumatic hypopituitarism was diagnosed in an 11-month-old male neutered cat. The presenting complaints were polydipsia, polyuria and lethargy of three months' duration. Craniocerebral trauma, as a result of a road traffic accident, had preceded the onset of clinical signs by six weeks. Neurological examination revealed right-sided mydriasis, reduced visual and tactile left forelimb placing reflexes and decreased proprioception in both the left fore- and hindlimb. Initial laboratory findings included hypernatraemia, hyperchloraemia, mild azotaemia, eosinophilia and isosthenuria. Low basal cortisol, thyroxine, thyroid-stimulating hormone and insulin growth factor-1 were noted. Subsequent to treatment with prednisolone, a water deprivation test confirmed the presence of central diabetes insipidus and therapy with synthetic antidiuretic hormone successfully ameliorated the polydipsia.

Accidents, Traffic↗
PubMed2004

Susceptibility to endotoxin induced uveitis is not reduced in mice deficient in BLT1, the high affinity leukotriene B4 receptor.

AIM: To investigate the role of arachidonic acid derived chemotactic factor, LTB(4), in the development of endotoxin induced uveitis (EIU), using mice deficient in the BLT1 gene which encodes the high affinity LTB(4) receptor. METHODS: BLT1 gene deficient and wild type BALB/c mice were injected intravitreally with Escherichia coli 055:B5 lipopolysaccharide (250 ng/2 microl). Number of leukocytes invading the anterior chamber 24 hours later were counted on tissue cross sections. RESULTS: In all mice, EIU was characterised by a polymorphonuclear and mononuclear cell infiltrate. Numbers of infiltrating cells did not differ significantly between control and BLT1 gene knockout mice. CONCLUSION: Chemotactic factors other than LTB(4) are primarily responsible for leukocyte migration into the eye during murine EIU.

Animals↗
PubMed2004

Use of corticosteroid sparing systemic immunosuppression for treatment of corticosteroid dependent optic neuritis not associated with demyelinating disease.

AIM: To describe the authors' experience and that in the published literature regarding the use of corticosteroid sparing systemic immunosuppression for patients with corticosteroid dependent optic neuritis not associated with demyelinating disease. METHODS: The records of 10 patients from the authors' clinical database, and 38 patients from the published literature with corticosteroid dependent optic neuritis, were retrospectively reviewed to determine patient demographics, diagnosis, clinical course, and outcomes. These patients had recrudescence of symptoms, such as decreased vision and pain, with attempted taper of corticosteroid. Many of these patients also suffered side effects from systemic corticosteroid use such as weight gain and uncontrolled hyperglycaemia. Antimetabolites (for example, methotrexate and azathioprine), cyclosporine and/or alkylating agents (for example, cyclophosphamide and chlorambucil) were given to enable taper of corticosteroid while effectively controlling optic neuritis. RESULTS: The study included 43 women and 5 men: 17 patients with systemic lupus erythematosus, 12 patients with sarcoidosis, 3 with other systemic autoimmune diseases, and 16 with no clinically identifiable systemic association. 79% of all patients benefited from the use of systemic immunosuppression in that they had successful corticosteroid taper, control of inflammation, improvement in symptoms, and/or tolerance of adverse effects. Mild toxicity was common and 19% of patients, most often those taking cyclophosphamide, discontinued medication because of adverse effects. 24 of 28 (86%) patients on alkylators benefited clinically, while 20 of 29 (69%) patients on antimetabolites had clinical benefit. CONCLUSION: Systemic immunosuppression may be a safer and more effective treatment alternative to chronic oral corticosteroid use in cases of corticosteroid dependent optic neuritis not associated with demyelinating disease.

Adrenal Cortex Hormones↗
PubMed2004

Neurological concomitants of uveitis.

AIM: To describe the prevalence and types of neurological disease that occur in association with uveitis. METHODS: Retrospective review of medical records of patients attending a tertiary referral uveitis service over a 15 year period. RESULTS: Of 1450 patients with uveitis, 115 (7.9%) had neurological disease that was considered to be causally related to the eye inflammation. The most frequent neurological associations were Vogt-Koyanagi-Harada disease, primary central nervous system lymphoma, multiple sclerosis, and herpes virus infections. CONCLUSIONS: Neurological disease is common among patients attending a uveitis service. The distinctive characteristics of the uveal inflammation may be useful in diagnosing the neurological disease.

Central Nervous System Neoplasms↗
PubMed2004

How do you know?

Explore the source record for details and available documents.

Biological Therapy↗
PubMed2004

Epilepsy in cortical dysplasia: factors affecting surgical outcome.

PURPOSE: To determine the factors influencing the outcome of cortical dysplasia resection for medically refractory epilepsy. MATERIAL AND METHODS: 13 patients underwent craniotomy for resection of epileptogenic foci using electrographic and MRI guidance. All patients had had seizures for more than 2 years and were on 3 or more antiepileptic medications. Their preoperative evaluation included MRI, neuropsychological evaluation including the WADA test, video EEG monitoring and intraoperative electrocorticography. Invasive preoperative monitoring was employed in 8 cases. The Engel outcome classification system was used. The mean follow-up time was 60.1 months with a minimum follow-up of 24 months. RESULTS: Postoperatively, all 6 patients younger than 18 years were seizure free. Among 7 patients older than 18 years, 6 were class II and 1 was class III. Based on their preoperative MRI studies, among the patients with abnormal studies, 2 were class I, 5 were class II and 1 was class III. Among patients with normal studies, 4 were class I and 1 class II. Regarding the ictal EEG findings, among patients with localizing findings, 4 were class I and 5 were class II. Among patients with no localization in their ictal EEG, 2 were class I, 1 class II and 1 class III. Regarding the invasive preoperative monitoring of the 7 patients with localizing findings, 5 were class I and 2 were class II. The only patient with nonlocalizing findings was class II. Finally, among the patients with no invasive preoperative monitoring, 3 were class I, 1 was class II and 1 was class III. CONCLUSION: Cortical resection is an effective treatment modality in patients with medically refractory epilepsy. In our series, the outcome was better in patients less than 18 years old and patients with normal preoperative MRI studies.

Adolescent↗
PubMed2003

The effect of maternal fasting on the fetal biophysical profile.

OBJECTIVES: To determine fetal biophysical profile changes in women observing Ramadan with uncomplicated singleton pregnancy. METHODS: In this cross-sectional observational study healthy women who were observing Ramadan at 30 weeks or more of gestation were recruited as well as a non-fasting control group matched for age, parity, and gestational age. Ultrasound examination included assessment of amniotic fluid volume, fetal bladder volume, fetal biophysical profile, and umbilical artery Doppler flow. RESULTS: A total of 162 pregnant women were observed. Mean umbilical artery pulsatility index, vertical amniotic pool depth, and fetal bladder volume were similar in the study and control groups. However, there was a significant difference in biophysical scores between the two groups. In the fasting group, 30 of 81 fetuses (37%) had a score of 6/8 compared with 11 of 81 fetuses (13.6%) in the control group (P=0.001). All fetuses in both groups with a biophysical score of 6/8 showed no breathing movements. CONCLUSIONS: Fetal breathing movements are reduced during maternal fasting.

Adult↗
PubMed2002

The determination of biperiden in plasma using gas chromatography mass spectrometry: pharmacokinetics after intramuscular administration to guinea pigs.

A gas chromatographic-mass spectrometric (GC-MS) method has been developed for the analysis of the biperiden from plasma. The method utilizes 290 microl of plasma and a simple hexane extraction/clean-up procedure. Standard curves were linear over the range of 1.9-250 ng/mL. The range of correlation coefficients for the individual standard curves was 0.9984-0.9999; the largest coefficient of variation expressed as a percentage (% CV) was 11.5%. Precision and accuracy were examined by assessing between-day and within-day variability. For between-day precision, the % CVs ranged from 2.86 to 5.17%. Accuracy as expressed by percentage error ranging from -2.16 to 5.83%. The study for within-day precision demonstrated % CVs from 0.95 to 5.55% with accuracy from -3.37 to 2.45%. Applicability of the method was demonstrated by examining the pharmacokinetics of intramuscular (i.m.) biperiden as an anticonvulsant treatment in a guinea pig model for organophosphate (OP)-induced seizure activity. Mean pharmacokinetic parameter estimates were similar to literature values; selected mean pharmacokinetic parameter estimates were: apparent volume of distribution, 13.9 L/kg; half-life of elimination, 93 min; time to maximal plasma concentration, 27.4 min; and maximal plasma concentration, 32.22 eta g/mL. The time to maximal plasma concentration was found to be similar to the onset time for terminating OP-induced seizure activity in guinea pigs receiving biperiden as an anticonvulsant treatment. The studies indicate that the method affords the required precision, accuracy and sensitivity to assay biperiden at the doses utilized for these pharmacokinetic studies after i.m. administration to guinea pigs.

Animals↗
PubMed2002

Toxicity assessment of sediments from the Grand Calumet River and Indiana Harbor Canal in Northwestern Indiana, USA.

The objective of this study was to evaluate the toxicity of sediments from the Grand Calumet River and Indiana Harbor Canal located in northwestern Indiana, USA. Toxicity tests used in this assessment included 10-day sediment exposures with the amphipod Hyalella azteca, 31-day sediment exposures with the oligochaete Lumbriculus variegatus, and the Microtox Solid-Phase Sediment Toxicity Test. A total of 30 sampling stations were selected in locations that had limited historic matching toxicity and chemistry data. Toxic effects on amphipod survival were observed in 60% of the samples from the assessment area. Results of a toxicity test with oligochaetes indicated that sediments from the assessment area were too toxic to be used in proposed bioaccumulation testing. Measurement of amphipod length after the 10-day exposures did not provide useful information beyond that provided by the survival endpoint. Seven of the 15 samples that were identified as toxic in the amphipod tests were not identified as toxic in the Microtox test, indicating that the 10-day H. azteca test was more sensitive than the Microtox test. Samples that were toxic tended to have the highest concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs). The toxic samples often had an excess of simultaneously extracted metals (SEM) relative to acid volatile sulfide (AVS) and had multiple exceedances of probable effect concentrations (PECs). Metals may have contributed to the toxicity of samples that had both an excess molar concentration of SEM relative to AVS and elevated concentrations of metals in pore water. However, of the samples that had an excess of SEM relative to AVS, only 38% of these samples had elevated concentration of metals in pore water. The lack of correspondence between SEM-AVS and pore water metals indicates that there are variables in addition to AVS controlling the concentrations of metals in pore water. A mean PEC quotient of 3.4 (based on concentrations of metals, PAHs, and PCBs) was exceeded in 33% of the sediment samples and a mean quotient of 0.63 was exceeded in 70% of the thirty sediment samples from the assessment area. A 50% incidence of toxicity has been previously reported in a database for sediment tests with H. azteca at a mean quotient of 3.4 in 10-day exposures and at a mean quotient of 0.63 in 28-day exposures. Among the Indiana Harbor samples, most of the samples with a mean PEC quotient above 0.63 ( i.e., 15 of 21; 71%) and above 3.4 ( i.e., 10 of 10; 100%) were toxic to amphipods. Results of this study and previous studies demonstrate that sediments from this assessment area are among the most contaminated and toxic that have ever been reported.

Animals↗
PubMed2002

An assessment of injury to sediments and sediment-dwelling organisms in the Grand Calumet River and Indiana Harbor Area of Concern, USA.

This article is the first in a series of three that describe the results of a Natural Resource Damage Assessment (NRDA) conducted in the Grand Calumet River and Indiana Harbor Area of Concern (IHAOC). The assessment area is located in northwest Indiana and was divided into nine reaches to facilitate the assessment. This component of the NRDA was undertaken to determine if sediments and sediment-dwelling organisms have been injured due to exposure to contaminants that have accumulated in sediments as a result of discharges of oil or releases of other hazardous substances from industrial, municipal, and nonpoint sources. To support this assessment, information was compiled on the chemical composition of sediment and pore water; on the toxicity of whole sediments, pore water, and elutriates; and on the status of benthic invertebrate communities. The data on each of these indicators were compared to regionally relevant benchmarks to assess the presence and extent of injury to surface water resources ( i.e., sediments) or biological resources ( i.e., sediment-dwelling organisms). The results of this assessment indicate that sediment injury has occurred throughout the assessment area, with up to four distinct lines of evidence demonstrating injury within the various reaches. The primary contaminants of concern ( i.e., those substances that are present at concentrations that are sufficient to cause or substantially contribute to sediment injury) include metals, polycyclic aromatic hydrocarbons, and total polychlorinated biphenyls.

Animal Diseases↗
PubMed2002

Assessment of injury to fish and wildlife resources in the Grand Calumet River and Indiana Harbor Area of Concern, USA.

This article is the second in a series of three that describes the results of a Natural Resource Damage Assessment (NRDA) conducted in the Grand Calumet River and Indiana Harbor Area of Concern (IHAOC). The assessment area is located in northwest Indiana and was divided into nine reaches to facilitate the assessment. This component of the NRDA was undertaken to determine if fish and wildlife resources have been injured due to exposure to contaminants that are associated with discharges of oil or releases of other hazardous substances. To support this assessment, information was compiled on the chemical composition of sediment and tissues; on the toxicity of whole sediments, pore water, and elutriates to fish; on the status of fish communities; and on fish health. The data on each of these indicators were compared to regionally relevant benchmarks to assess the presence and extent of injury to fish and wildlife resources. The results of this assessment indicate that injury to fish and wildlife resources has occurred throughout the assessment area, with up to five distinct lines of evidence demonstrating injury within the various reaches. Based on the frequency of exceedance of the benchmarks for assessing sediment and tissue chemistry data, total polychlorinated biphenyls is the primary bioaccumulative contaminant of concern in the assessment area. It is important to note, however, that this assessment was restricted by the availability of published bioaccumulation-based sediment quality guidelines, tissue residue guidelines, and other benchmarks of sediment quality conditions. The availability of chemistry data for tissues also restricted this assessment in certain reaches of the assessment area. Furthermore, insufficient information was located to facilitate identification of the substances that are causing or substantially contributing to effects on fish (i.e., sediment toxicity, impaired fish health, or impaired fish community structure). Therefore, substances not included on the list of COCs cannot necessarily be considered to be of low priority with respect to sediment injury (e.g., metals, polycyclic aromatic hydrocarbons, alkanes, alkenes, organochlorine pesticides, phthalates, dioxins, and furans, etc.).

Animals↗
PubMed2002

Lamellar subcomponents of the cuticular cell membrane complex of mammalian keratin fibres show friction and hardness contrast by AFM.

There is a substantial body of information indicating that 18-methyleicosanoic acid (18-MEA) is covalently linked to the outer surface of all mammalian keratin fibres and also forms the outer beta-layer of the cuticular cell membrane complex (CCMC) which separates the cuticle cells from each other. Low cohesive forces are expected between the lipid-containing outer beta-layer and the delta-layer of the CCMC, thus providing a weak point for cuticular delamination and presenting a fresh layer of 18-MEA to the newly exposed surface. We have used lateral force microscopy and force modulation atomic force microscopy (AFM) to examine human hair fibres in which the non-covalently linked fatty acids have been removed. Examination of the lateral force images of new cuticle surfaces revealed by the attrition of overlying cuticle layers showed three separate zones of clearly defined frictional contrast. These are thought to correspond with the delta-layer, the proteinaceous epicuticle and outer beta-layers of the CCMC. The delta-layer was found to have a thickness of 16 nm (SD = 1 nm, n = 25), comparable to the 18.0 nm thickness measured from transverse cross-sections of fibres with transmission electron microscopy. Force modulation AFM showed that the outer beta-layer was softer than the epicuticle and the delta-layer. The frictional contrast was removed following treatment with methanolic KOH (0.1 mol dm-3) at 25 degrees C for 30 min, suggesting the hydrolysis of the thioester linkage and removal of 18-MEA from the surface.

Animals↗
PubMed2002

Iris nodules associated with infectious uveitis.

BACKGROUND/AIM: Iris nodules are an uncommon clinical sign in uveitis. The diseases most commonly associated with iris nodules and uveitis include sarcoidosis, Vogt-Koyanagi-Harada syndrome, multiple sclerosis, Fuchs' heterochromic iridocyclitis, and metastatic infection. While many of these diseases may be appropriately treated with immunosuppressive medication, the management of infectious uveitis is antimicrobial therapy. Inappropriate immunosuppressive therapy may result in a poor outcome for the patient with an infection. Consequently, cases of uveitis with iris nodules were reviewed to identify clinical features that may help differentiate infection from non-infectious inflammation. METHODS: The clinical database of 1353 consecutive patients evaluated at a tertiary care referral based North American uveitis clinic were retrospectively reviewed to identify cases of infectious uveitis with iris nodules. A Medline search was performed to identify additional cases. From these cases information regarding clinical presentation, diagnosis, treatment, and outcome were collected. RESULTS: Three cases (three eyes) were identified from the authors' own records of infectious uveitis with iris nodules. An additional 25 cases of infectious uveitis with iris nodules were identified in 22 published reports. Analysis of the authors' cases and these reports showed that infectious uveitis with iris nodules was specifically characterised by some or all of the following: (1) creamy, soft appearance to the nodule(s), (2) unilateral disease, (3) persistence or growth of the nodule(s) despite corticosteroid therapy, (4) marked inflammatory response in the anterior chamber and/or vitreous humour, and/or (5) history suggesting a potential source of septic emboli. CONCLUSION: Certain features of the clinical history and examination are useful in the diagnosis of metastatic infection in patients presenting with uveitis and iris nodules.

Adult↗
PubMed2001

A giant sauropod dinosaur from an Upper Cretaceous mangrove deposit in Egypt.

We describe a giant titanosaurid sauropod dinosaur discovered in coastal deposits in the Upper Cretaceous Bahariya Formation of Egypt, a unit that has produced three Tyrannosaurus-sized theropods and numerous other vertebrate taxa. Paralititan stromeri is the first tetrapod reported from Bahariya since 1935. Its 1.69-meter-long humerus is longer than that of any known Cretaceous sauropod. The autochthonous scavenged skeleton was preserved in mangrove deposits, raising the possibility that titanosaurids and their predators habitually entered such environments.

Animals↗
PubMed2001

Contrasting roles of p57(KIP2) and p21(WAF1/CIP1/SDI1) in transplanted human and bovine adrenocortical cells.

Cell transplantation provides a way to compare the regulation of cell proliferation in the same cell type in cell culture and in a vascularized tissue structure in a host animal. The cyclin-dependent kinase inhibitors p57(KIP2), p21(WAF1/CIP1/SDI1) and p27(KIP1) have been extensively studied in cell culture but their role in growth control in tissues is less well understood. In the present experiments we compared the behavior of cell cycle inhibitors in human and bovine adrenocortical cells in culture and following cell transplantation in scid mice. p57 was expressed in the majority of cells in the intact human adrenal cortex. However, double immunofluorescence showed that cells that are in the cell cycle are p57(-) adrenocortical cells, p57 and p27 levels were not affected by inhibition of growth at high cell density, whereas p21 was higher in dividing than growth-inhibited cells. However, p21 was also high in senescent adrenocortical cells. After transplantation of human adrenocortical cells in scid mice, p57 and p27 were observed in most cells in the transplant tissue. Over time the number of p21(+) cells decreased greatly in human adrenocortical cells, but not in bovine adrenocortical cells. This difference correlated with lower levels of cell division (assessed by Ki-67 or incorporation of bromodeoxyuridine) in the human cells in transplant tissues in comparison to bovine cells. The differences between human and bovine cells were observed both when cells were transplanted beneath the kidney capsule and when cells were injected subcutaneously in collagen gel. We conclude that the behavior of p57, but not p21, is consistent with a role as a physiological mediator of proliferative quiescence in the adrenal cortex. The high level of p21 in dividing adrenocortical cells in culture, and in bovine adrenocortical cells in transplant tissues, may be a response to conflicting positive and negative growth influences. Cells may enter the cell cycle under the influence of a strong positive mitogenic signal, but coexisting negative growth stimuli trigger a p21-dependent block to further progression through the cell cycle. This model suggests that bovine adrenocortical cells respond to positive growth stimuli in transplant tissues but human cells lack this response.

Adolescent↗
PubMed2001

DNA methyltransferase inhibition in normal human fibroblasts induces a p21-dependent cell cycle withdrawal.

Maintenance of methylation patterns in the mammalian genome by DNA (cytosine-5) methyltransferases (DNAMeTase) is required for normal cell and tissue function. Inhibition of DNAMeTase in cultured cells induces the expression of p21, a cyclin-dependent kinase (Cdk) inhibitor critical for cells to enter replicative senescence. We investigated the effects of DNAMeTase inhibition in normal human fibroblasts and found that it induces an irreversible growth arrest. Cells arrested by DNAMeTase inhibition became enlarged and had a flat morphology, exhibited an increased expression of collagenase and p21, and the DNA synthesis block could be overcome by the introduction of the SV40 large T antigen, all characteristics of senescent cells. In contrast, normal human fibroblasts lacking a functional p21 gene fail to undergo cell cycle arrest following DNAMeTase inhibition, indicating that p21 is an essential component of this arrest. Furthermore, DNAMeTase activity was reduced as cells approached the end of their proliferative potential. These data suggest that DNAMeTase could be an integral part of the mechanisms by which cells count the number of cell divisions completed and initiate a signaling cascade that ultimately results in the senescent phenotype.

Blotting, Northern↗