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Biomedical subjects

G Harris

Publications and source records attributed to G Harris.

At least 91 records · Page 5Linked to original sources
PubMed1994

Idiopathic sclerosing inflammation of the orbit. A distinct clinicopathologic entity.

BACKGROUND: Idiopathic sclerosing inflammation of the orbit is a poorly delineated, fibrosing, immune-mediated entity resulting in significant ocular disability. To characterize this process and propose more specific and effective therapy, clinical and pathologic findings in 16 cases are reviewed. METHODS: The clinical records of 16 patients with biopsy-proven disease were retrospectively reviewed to determine demographic and clinical features, radiologic features, course, management, and outcome. These findings were correlated with pathologic features to describe this unique entity. Immunohistologic characteristics were compared with those of a clinically and histopathologically similar process, retroperitoneal fibrosis. RESULTS: The study included 11 male and 5 female patients, ranging in age from 8 to 81 years. Disease onset was usually unilateral (14/16) and chronic (11/15), with two distinct anatomic presentations, lacrimal (11/16) and apical (3/16), characterized by infiltration (15/16), mass effect (12/16), and visual loss (3/16). The most common signs and symptoms were dull pain (13/16), proptosis (11/16), mild inflammation (11/16), restricted motility (9/16), swelling (9/16), and diplopia (8/16). Two features, a sparse, chronic inflammatory infiltrate, the immunopathologic characteristics of which suggested a cell-mediated process, and a desmoplastic stroma of early onset, dominated the pathologic picture. Treatment with corticosteroids (11/16), radiotherapy for steroid failures (8/11), and observation alone (3/16) was inadequate, resulting in blindness in 3/16 cases, restricted movement in 10/16, and complete resolution in only 2/16 patients. CONCLUSION: Idiopathic sclerosing inflammation of the orbit is a unique clinicopathologic entity, similar to retroperitoneal fibrosis, that is characterized by primary, chronic, and immunologically mediated fibrosis, poor response to corticosteroid treatment or radiotherapy, and frequent visual disability. Early and aggressive immunosuppressive therapy is recommended.

Adolescent↗
PubMed1994

Prospective review of 278 endoscopic carpal tunnel releases using the modified chow technique.

The results of 278 endoscopic carpal tunnel releases using the extrabursal dual portal Chow technique were analyzed prospectively. The majority of patients were pain free by the 57th postoperative day. The perioperative complication rate was 1.7%. The late complication rate was 2.8%. Two cases were converted to open carpal tunnel release. The average time to return to full-duty work was 65 days in those patients covered by worker's compensation, whereas it was 21 days in the privately insured (non-worker's compensation) patients. The endoscopic release of the transverse carpal ligament is an effective technique for the treatment of carpal tunnel syndrome with a low complications rate. Return to full employment requires more time in those patients covered by worker's compensation.

Adult↗
PubMed1994

The structure of Bacillus subtilis pectate lyase in complex with calcium.

We have solved the structure of the Bacillus subtilis pectate lyase (BsPel) in complex with calcium. The structure consists of a parallel beta-helix domain and a loop region. The alpha L-bounded beta-strand seen in BsPel is a new element of protein structure and its frequent occurrence suggests it is an important characteristic of the parallel beta-helix. A pronounced cleft is formed between the loops and the parallel beta-helix domain and we propose that this is the active site cleft. Calcium, essential for the activity of the enzyme, binds at the bottom of this cleft and an arginine residue close to the calcium, which is conserved across all pectin and pectate lyases, may be involved in catalysis.

Amino Acid Sequence↗
PubMed1994

7,8-Dihydro-8-oxo-2'-deoxyguanosine present in DNA is not simply an artefact of isolation.

7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) is present in DNA isolated from human and murine cells. Other studies have reported artificially elevated levels in DNA extracted using phenol-based methods. This report shows that DNA, isolated by different methods, with or without the use of a phenol reagent, contains similar levels of 8-oxodG. This, taken with other studies of human tissues which show varying levels of 8-oxodG, indicates that, with due care in the extraction procedure, biologically significant amounts of this altered base are present in mammalian DNA.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

The susceptibility of inbred mice to the production of malignant thymoma by N-methyl-N-nitrosourea.

The susceptibility of inbred mice to the induction of malignant thymoma by N-methyl-N-nitrosourea (MNU) has been quantified and compared. Strain differences emerged and this was also apparent in congenic lines of C57BL/10 mice, differing at the H-2 locus. However, different strains of inbred mice, with identical H-2 haplotypes, also showed varying susceptibility to MNU, indicating that the role of the MHC was not a simple one, but apparently depended on other, undefined genes. Proficiency of repair of O6-methylguanine by thymic tissue was not responsible for these strain differences and the increased resistance to induction of thymoma by MNU in older mice was due to age-dependent changes within the thymus gland. Interestingly, the thymus of older mice, grafted with neonatal thymic tissue, still provided a suitable environment for the development of thymic tumours.

Age Factors↗
PubMed1994

Feeding problems in young PKU children.

Behavioural feeding problems were found to be more prevalent in a group of 15 PKU children aged 1-5 years when compared to non-PKU controls. The parents of PKU children identified poorer apatites (p < 0.01), a more limited range of foods consumed (p < 0.03) and more gastrointestinal symptoms such as vomiting and constipation (p < 0.03) than control children. The children were slower to feed (p < 0.03), were more likely to dislike sweet foods and some ate separately from the rest of the family at mealtime (p < 0.03). The effects on normal feeding behaviour should be considered when advocating strict diet therapy for young PKU children.

Case-Control Studies↗
PubMed1993

Antilipid a monoclonal antibody HA-1A: immune complex clearance of endotoxin reduces TNF-alpha, IL-1 beta and IL-6 production.

HA-1A is a human monoclonal IgM antibody which recognizes the lipid A component of lipopolysaccharide (LPS). This antibody has reduced mortality in the septic shock syndrome resulting from Gram negative bacteria, in which many of the manifestations are considered to be due to cellular activation and secretion of cytokines, most notably TNF-alpha. However HA-1A does not directly neutralize LPS effectively in vitro, and studies reported to date have not defined its mechanism of action. Here we demonstrate that HA-1A, which in the presence of complement promotes immune adherence, may inhibit LPS action by facilitating its sequestration on red blood cells and clearance to an extent that cytokine production is reduced. Incubation of LPS at clinically significant (pg/ml) does with HA-1A at therapeutic levels (e.g. 10 micrograms/ml) and complement resulted in LPS association with erythrocyte CR1 receptors. This reduced the ability of the residual, free LPS by 50-70% to induce the secretion of TNF-alpha, IL-1 beta and IL-6 from normal blood mononuclear cells. This mechanism is likely to be operative in vivo, and could account for the protective effect of HA-1A, and its reduction of TNF-alpha production in vivo.

Antibodies, Monoclonal↗
PubMed1993

Antilipid A monoclonal antibody HA-1A decreases the capacity of bacterial lipopolysaccharide to activate human vascular endothelial cells by an immune adherence mechanism.

Human monoclonal IgM antibody HA-1A, which recognizes the lipid A component of bacterial lipopolysaccharide (LPS), has been shown to reduce mortality in Gram negative septicemia. The vascular endothelial lining of blood vessels, which controls leucocyte traffic and activation, as well as haemostatic balance, may be one of the primary targets of LPS action during sepsis. In earlier studies we have described HA-1A-induced immune adherence of LPS to complement receptors on erythrocytes, and showed that pre-incubation with HA-1A, in the presence of complement and red blood cells, markedly reduced LPS-induced cytokine production from peripheral blood mononuclear cells. In the present study, we measured the effect of immune adherence of LPS in the presence of HA-1A on the responses of cultured endothelial cells, and found that subsequent expression of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and secretion of the cytokines interleukin-6 and granulocyte-macrophage colony stimulating factor were markedly reduced. Moreover, the ability of LPS to increase levels of tissue factor procoagulant activity on endothelial cells was markedly diminished by LPS immune adherence to HA-1A. This decrease in endothelial activation in response to LPS following immune adherence to HA-1A may play a significant role in the protective effect of HA-1A in vivo during the course of Gram negative sepsis.

Antibodies, Monoclonal↗
PubMed1993

Intraoral palatal mucosal graft harvest.

The anatomy of the hard plate is reviewed with respect to the clinical considerations of harvesting intraoral hard palate grafts for various reconstructive eyelid procedures. Recommendations for harvesting grafts based on these anatomic principles are given.

Eyelids↗
PubMed1993

Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases.

OBJECTIVES: To estimate the extent of genomic DNA damage and killing of lymphocytes by reactive oxygen intermediates in autoimmune diseases. METHODS: 8-Oxo-7-hydrodeoxyguanosine (8-oxodG), a promutagenic DNA lesion induced by reactive oxygen intermediates, was measured by high performance liquid chromatography, coupled with electrochemical detection, in hydrolysates of DNA which had been extracted from lymphocyte and polymorphonuclear leucocyte fractions of human blood. In addition, human primary blood lymphocytes stimulated by concanavalin A were assayed for cytotoxicity induced by hydrogen peroxide on day 0, by assessing cell proliferation during seven days of culture. RESULTS: Constitutive 8-oxodG was detectable (mean (2 SEM) moles 8-oxodG/10(6) moles deoxyguanosine) in DNA isolated from normal human blood lymphocytes (68 (8), n = 26) and polymorphonuclear leucocytes (118 (24), n = 24). Lymphocyte DNA from donors with the following inflammatory autoimmune diseases contained significantly higher levels of 8-oxodG than that from healthy donors: rheumatoid arthritis (98 (16)), systemic lupus erythematosus (137 (28)), vasculitis (100 (32)), and Behçet's disease (92 (19)). Lymphocyte 8-oxodG levels in non-autoimmune controls and patients with scleroderma were not significantly different from those of healthy controls. The levels of 8-oxodG were significantly higher in the DNA from normal polymorphonuclear leucocytes than in paired DNA samples from normal lymphocytes, but there were no differences between levels of 8-oxodG in polymorphonuclear leucocytes from normal subjects and the patients studied. Levels of 8-oxodG did not correlate with disease duration, disease severity, or age. Lymphocytes from patients with systemic lupus erythematosus and rheumatoid arthritis, but not those with scleroderma, also showed cellular hypersensitivity to the toxic effects of hydrogen peroxide. CONCLUSION: There was increased genomic DNA damage, and increased susceptibility to cytotoxic killing by hydrogen peroxide, in lymphocytes from patients with certain autoimmune diseases. These results might be explained by defective repair of DNA damage or by increased production of reactive oxygen intermediates in inflammation. Although more direct studies are needed, the evidence available favours the former explanation.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1993

Voxel processing techniques for the antemortem study of neuroanatomy and neuropathology using magnetic resonance imaging.

BRAINBLAST, a program that uses voxel processing, was developed in order to produce high-fidelity three-dimensional reconstructions of the brain. Four steps were used to produce images: washing away cerebrospinal fluid (via histogramming), dissecting away the blood vessels (via a connectivity heuristic), highlighting the sulci and gyri (via a lighting model), and resampling the interior contents of the brain. After reconstruction, the images can be resampled, rotated, written on, measured, or redissected. The technique has a variety of applications: study of individual variation in sulcal and gyral patterns, evaluation of structure/function relationships, measurement of volumes or subregions using anatomically defined landmarks, and teaching of neuroanatomy.

Brain↗
PubMed1993

Idiopathic sclerosing inflammation of the orbit: immunohistologic analysis and comparison with retroperitoneal fibrosis.

Idiopathic sclerosing inflammation of the orbit is clinically characterized by an insidious, chronic and progressive fibrosing process damaging orbital structures through entrapment and mass effect. Histologically, desmoplasia and a sparse infiltrate of lymphocytes, histiocytes, plasma cells, and occasional neutrophils and eosinophils are seen. An immune pathogenesis is suspected but presently poorly understood. To characterize the inflammatory infiltrate and to compare orbital and other inflammatory fibrosing lesions, immunoperoxidase studies using the streptavidin method were performed on 16 formalin or Bouins' fixed, paraffin-embedded orbital biopsy specimens and six specimens of retroperitoneal fibrosis. Positive staining of orbital tissue occurred as follows: T-cells (UCHL-1) 94% of cases, B-cells (L26) 40%, tissue macrophages (KP-1) 56%, HLA Dr positive antigen presenting cells and activated T-cells (LN3) 44%, and immunoglobulins (kappa, 80%; lambda, 63%, IgG, 73%, IgA, 44% and IgM, 31%). Results were strikingly similar for retroperitoneal fibrosis. These findings imply a cell mediated pathogenesis in idiopathic sclerosing inflammation of the orbit that is similar to retroperitoneal fibrosis and suggest therapeutic potential for agents modifying this facet of the immune system.

Humans↗
PubMed1993

Automated iterative three-dimensional registration of positron emission tomography images.

Two types of image similarity measures, the sum of absolute differences (SAD) and the stochastic sign change (SSC), were compared for three-dimensional registration of images from PET. To test the accuracy of both registration methods, 30 FDG brain studies, 40 13N-ammonia cardiac studies and 20 FDG liver tumor studies (where each image set contained 15 image planes, 128 x 128 pixels per plane) were made into worse case conditions by creating image sets of low counts and extreme defects. These images were then registered to the reference images that had been moved in three dimensions into a random set of known translations, rotations and normalization factors (x, y, z, theta, rho, sigma, nf). Neither method required any external fiduciary markers or operator interventions to register a set of images. The optimization of the image similarity (using the SAD or SSC) was performed with the simplex method and registration was completed within 10 min of computation time on a low-end workstation. Overall, the SAD method had an average inplane (x, y) registration error of 0.5 +/- 0.5 mm, a z-axis registration error of 1.1 +/- 1.1 mm, an inplane rotational error of 0.5 +/- 0.4 degrees, an out-of-plane rotational error of 1.1 +/- 1.2 degrees and a normalization factor error of 0.015 +/- 0.016. The SSC method had an average inplane (x, y) registration error of 0.6 +/- 0.5 mm, a z-axis registration error of 1.1 +/- 1.1 mm, an inplane rotational error of 0.7 +/- 0.5 degrees, an out-of-plane rotational error of 1.0 +/- 1.2 degrees and a normalization factor error of 0.014 +/- 0.014. This study demonstrates that either the SAD or SSC method for measuring image similarity, combined with the simplex method for function optimization, are accurate methods for registration of a wide variety of PET images including low count studies and those with marked interval changes in the pattern of count distribution.

Brain↗
PubMed1993

Feeding iron-fortified premature formula during initial hospitalization to infants less than 1800 grams birth weight.

OBJECTIVE: A randomized, double-blind study was conducted comparing high-iron content (15 mg/L) with low-iron content (3 mg/L) premature formula given during initial hospitalization to infants with birth weights less than 1800 g to determine the influence of these differing intakes on the iron nutritional status during the first 4 months of life. A third group of similar infants received human milk mixed with an equal volume of liquid fortifier resulting in an iron content of approximately 1.7 mg/L. PATIENTS AND METHODS: Mean birth weight, gestational age, age at study entry, volume of blood removed for studies, and volume of red cells transfused were not different among the three groups. After hospitalization both formula-fed groups were given a cow milk formula with an iron content of 12 mg/L, and breast-fed infants were given an iron-containing multivitamin with a resulting iron intake of 10 mg/d. Infants were observed to 8 weeks after discharge. RESULTS: There were no differences in serum iron, ferritin, transferrin, transferrin saturation, hemoglobin, hematocrit, or reticulocyte count among the three groups at study entry, although mean corpuscular hemoglobin and mean corpuscular volume were lower in infants in the low-iron formula group. Mean plasma ferritin was significantly lower in infants receiving low-iron content premature formula at the time of hospital discharge compared with the other two groups. The incidence of anemia (hemoglobin < 9.0 g/dL) and low transferrin saturation (< 24%) was also greater in the low-iron content formula group. Eight weeks after discharge, the incidence of low plasma ferritin (< 19 ng/mL) remained greater in infants receiving low-iron content formula than in the other two groups. No adverse effects of iron intake were observed. Growth was not different among the three groups. CONCLUSIONS: These data indicate that preterm infants with < 1800 g birth weight receiving premature infant formula benefit from formula given during initial hospitalization containing 15 mg/L iron compared with that containing 3 mg/L.

Anemia, Hypochromic↗