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V Thompson

Publications and source records attributed to V Thompson.

At least 19 recordsLinked to original sources
PubMed1999

Chondrocyte-mediated catabolism of aggrecan: evidence for a glycosylphosphatidylinositol-linked protein in the aggrecanase response to interleukin-1 or retinoic acid.

The control of chondrocyte-mediated degradation of aggrecan has been studied in rat chondrosarcoma cells and bovine cartilage explants treated with either IL-1 or retinoic acid. The capacity of glucosamine to inhibit the aggrecanase-mediated response (J. D. Sandy, D. Gamett, V. Thompson, and C. Verscharen (1998) Biochem. J. 335, 59-66) has been extended to an investigation of the effect of other hexosamines. Mannosamine inhibits the aggrecanase response to both IL-1 and RA at about one-tenth the concentration of glucosamine in both rat cell and bovine explant systems. This effect of mannosamine appears to be due to its capacity to inhibit the synthesis of glycosylphosphatidylinositol (GPI)-linked proteins by chondrocytes since the GPI synthesis inhibitor 2-deoxyfluoroglucose (2-DFG) also inhibited the aggrecanase response to IL-1b and RA in rat cells. Moreover, phosphatidylinositol-specific phospholipase C (PIPLC) treatment of rat cells markedly inhibited the aggrecanase response to IL-1b and RA. These inhibitory effects of mannosamine, 2-DFG, and PIPLC in rat cells did not appear to be due to an interference with general biosynthetic activity of the cells as measured by [3H]proline incorporation into secreted proteins. We suggest that the aggrecanase response by chondrocytes to IL-1 and RA is dependent on the activity of a GPI-anchored protein on the chondrocyte cell surface.

Aggrecans↗
PubMed1998

Chondrocyte-mediated catabolism of aggrecan: aggrecanase-dependent cleavage induced by interleukin-1 or retinoic acid can be inhibited by glucosamine.

A rat chondrosarcoma cell line and bovine cartilage explants have been used to study the control of aggrecan degradation by chondrocytes treated with interleukin-1 (IL-1) or retinoic acid (RA). Aggrecan fragment analysis with anti-neo-epitope antibodies suggests that aggrecanase (an as yet unidentified enzyme) is the only aggrecan-degrading proteinase active in these cultures. With rat cells, aggrecanase converts the aggrecan core protein into two major G1-domain-bearing products (60 kDa with a C-terminal Glu-373, and 220 kDa with a C-terminal Glu-1459). Both products were quantified on a standardized Western analysis system with a G1-specific antibody. Immunoblots were analysed by scanning densitometry and the sensitivity, linearity and reproducibility of the assay were established. With rat cells the aggrecanase response to IL-1 was optimal at about 2 mM glutamine, but was progressively inhibited at higher concentrations, with about 90% inhibition at 10 mM glutamine. Such inhibition by glutamine was not, however, observed with bovine explants. On the other hand, marked inhibition of aggrecanase-dependent cleavage was observed with both rat cells and bovine explants when d(+)-glucosamine was included at concentrations above 2 mM. Inhibition was apparently not due to cytotoxicity or interference with IL-1 signalling, since biosynthetic activity was not inhibited and inhibition of the aggrecanase response was also obtained when RA was used as the catabolic stimulator. Possible mechanisms for the inhibition of the aggrecanase response by glucosamine in chondrocytes treated with IL-1 or RA are discussed.

Aggrecans↗
PubMed1998

Portal imaging protocol for radical dose-escalated radiotherapy treatment of prostate cancer.

PURPOSE: The use of escalated radiation doses to improve local control in conformal radiotherapy of prostatic cancer is becoming the focus of many centers. There are, however, increased side effects associated with increased radiotherapy doses that are believed to be dependent on the volume of normal tissue irradiated. For this reason, accurate patient positioning, CT planning with 3D reconstruction of volumes of interest, clear definition of treatment margins and verification of treatment fields are necessary components of the quality control for these procedures. In this study electronic portal images are used to (a) evaluate the magnitude and effect of the setup errors encountered in patient positioning techniques, and (b) verify the multileaf collimator (MLC) field patterns for each of the treatment fields. METHODS AND MATERIALS: The Phase I volume, with a planning target volume (PTV) composed of the gross tumour volume (GTV) plus a 1.5 cm margin is treated conformally with a three-field plan (usually an anterior field and two lateral or oblique fields). A Phase II, with no margin around the GTV, is treated using two lateral and four oblique fields. Portal images are acquired and compared to digitally reconstructed radiographs (DRR) and/or simulator films during Phase I to assess the systematic (CT planning or simulator to treatment error) and the daily random errors. The match results from these images are used to correct for the systematic errors, if necessary, and to monitor the time trends and effectiveness of patient imobilization systems used during the Phase I treatment course. For the Phase II, portal images of an anterior and lateral field (larger than the treatment fields) matched to DRRs (or simulator images) are used to verify the isocenter position 1 week before start of Phase II. The Portal images are acquired for all the treatment fields on the first day to verify the MLC field patterns and archived for records. The final distribution of the setup errors was used to calculate modified dose-volume histograms (DVHs). This procedure was carried out on 36 prostate cancer patients, 12 with vacuum-molded (VacFix) bags for immobilization and 24 with no immobilization. RESULTS: The systematic errors can be visualized and corrected for before the doses are increased above the conventional levels. The requirement for correction of these errors (e.g., 2.5 mm AP shift) was demonstrated, using DVHs, in the observed 10% increase in rectal volume receiving at least 60 Gy. The random (daily) errors observed showed the need for patient fixation devices when treating with reduced margins. The percentage of fields with displacements of < or = 5.0 mm increased from 82 to 96% with the use of VacFix bags. The rotation of the pelvis is also minimized when the bags are used, with over 95% of the fields with rotations of < or = 2.0 degrees compared to 85% without. Currently, a combination of VacFix and thermoplastic casts is being investigated. CONCLUSION: The systematic errors can easily be identified and corrected for in the early stages of the Phase I treatment course. The time trends observed during the course of Phase I in conjunction with the isocenter verification at the start of Phase II give good prediction of the accuracy of the setup during Phase II, where visibility of identifiable structures is reduced in the small fields. The acquisition and inspection of the portal images for the small Phase I fields has been found to be an effective way of keeping a record of the MLC field patterns used. Incorporation of the distribution of the setup errors into the planning system also gives a clearer picture of how the prescribed dose was delivered. This information can be useful in dose-escalation studies in determining the relationship between the local control or morbidity rates and prescribed dose.

Humans↗
PubMed1997

Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome.

Loss-of-function mutations in the G4.5 gene have been shown to cause Barth syndrome (BTHS), an X-linked disorder characterized by cardiac and skeletal myopathy, short stature, and neutropenia. We recently reported a family with a severe X-linked cardiomyopathy described as isolated noncompaction of the left ventricular myocardium (INVM). Other findings associated with BTHS (skeletal myopathy, neutropenia, growth retardation, elevated urinary organic acids, and mitochondrial abnormalities) were either absent or inconsistent. A linkage study of the X chromosome localized INVM to the Xq28 region near the BTHS locus, suggesting that these disorders are allelic. We screened the G4.5 gene for mutations in this family with SSCP and direct sequencing and found a novel glycine-to-arginine substitution at position 197. This position is conserved in a homologous Caenorhabditis elegans protein. We conclude that INVM is a severe allelic variant of BTHS with a specific effect on the heart. This finding provides further structure-function information about the G4.5 gene product and has implications for unexplained cases of severe infantile hypertrophic cardiomyopathy in males.

Abnormalities, Multiple↗
PubMed1996

A prospective multicenter trial of excimer laser phototherapeutic keratectomy for corneal vision loss. The Summit Phototherapeutic Keratectomy Study Group.

PURPOSE: The 193-nm argon fluoride excimer laser can remove corneal scars and smooth corneal irregularities, obviating corneal transplantation. We conducted a prospective multicenter trial of excimer laser phototherapeutic keratectomy for corneal vision loss as a basis for Food and Drug Administration premarket approval. METHODS: We treated 232 eyes of 211 patients with corneal vision loss. All had corneal pathology in the anterior 100 microns of the stroma. Mean postoperative follow-up was 10 +/- 8 months. The primary outcome variable was change in best spectacle-corrected visual acuity. RESULTS: At postoperative month 12, best spectacle-corrected visual acuity improved in 46 (45%) of 103 eyes and worsened in nine (9%) of 103 eyes by 2 or more Snellen lines. Best spectacle-corrected visual acuity improved by a mean of 1.6 +/- 2.8 Snellen lines (95% confidence interval, 1.1 to 2.1 lines). Every postoperative visit confirmed statistically significant improvement of mean best spectacle-corrected acuity. At month 12, treated eyes had a mean hyperopic shift in refraction of 0.87 diopter and a mean reduction in astigmatism of 0.36 diopter. Treatment appeared most effective in eyes with hereditary corneal dystrophies, Salzmann's nodular degeneration, and corneal scars, and least effective in eyes with calcific band keratopathy. Complications included recurrence of underlying pathology, corneal graft rejection, and bacterial keratitis. CONCLUSIONS: Argon fluoride excimer laser phototherapeutic keratectomy is effective, with relatively few complications, for treating vision loss from corneal opacification or irregularity. Efficacy, however, varies widely depending upon individual eyes and underlying diagnoses.

Adult↗
PubMed1996

Pictorial review: comparison of portal imaging and megavoltage verification films for conformal pelvic irradiation.

This study has evaluated the use of electronic portal imaging (EPI) as a replacement for megavoltage verification films in the treatment of conformal pelvic patients. The two methods of imaging have been compared in 40 patients. Several advantages of EPI were identified, including case of image acquisition. regular assessment of reproducibility of set-up and the possibility of on-line intervention when necessary. The findings suggest that EPI is a suitable replacement for films.

Humans↗
PubMed1995

In situ lymphoproliferation in renal transplant biopsies.

A double immunohistochemical labelling procedure in paraffin-embedded renal tissue is reported in which CD3 was targeted as a T cell marker and Ki67 as a marker of cell proliferation. Proliferating and quiescent T cells were unequivocally identified in situ, and their precise location within the kidney was clarified by the use of periodic acid-Schiff counterstaining to outline the basement membranes. Proliferating tubular epithelial cells were also clearly identified. The results showed that T lymphocytes proliferate within the tubular compartment during acute renal allograft rejection. Preliminary evaluation of the method in routine transplant biopsies indicated significant correlations between histologically defined rejection grade and mean intratubular T lymphocytes per tubular cross section and between proliferation of tubular epithelial cells and of intratubular T lymphocytes. The associated tubular epithelial cell proliferation may be a response to local damage.

Antigens, Differentiation↗
PubMed1995

Use of in situ detection of histone mRNA in the assessment of epidermal proliferation: comparison with the Ki67 antigen and BrdU incorporation.

The labelling index is commonly used as a measure of proliferation. However, the use of tritiated thymidine or BrdU labelling of S-phase cells is limited to prospective samples. We have employed an oligonucleotide cocktail complementary to the mRNA species encoding the replication-dependent histones H2B, H3 and H4 for non-isotopic in situ hybridization (NISH), and have compared the resultant proliferation indices in normal skin with those obtained by bromodeoxyuridine (BrdU) incorporation and by Ki67 immunohistochemistry (IHC) using the monoclonal antibody MIB1. In addition, we compared the staining characteristics of histone NISH and Ki67 IHC in a further 25 samples from a variety of inflammatory dermatoses and neoplastic conditions, as well as from normal skin. In normal skin, S-phase (histone NISH and BrdU) and cycling (Ki67) cells were confined to the basal and low suprabasal layers. The labelling indices determined by histone NISH and BrdU incorporation were similar, whereas that of Ki67 IHC was four times greater. In biopsies from hyperproliferative dermatoses and dysplastic or malignant lesions, the number of histone NISH- and Ki67 IHC-positive cells was generally elevated; in accordance with the differential expression of these two markers during the cell cycle, MIB1 consistently gave higher results. The advantage of histone NISH over Ki67 IHC is that it is a marker of the same part of the cell cycle as BrdU incorporation. However, the combined use of both histone NISH and Ki67 IHC to measure two cell cycle parameters, namely S-phase and the number of cycling cells, allows more detailed retrospective study of epidermal proliferation than has been possible previously.

Bowen's Disease↗
PubMed1995

Violence in the marital dyad as a predictor of violence in the peer relationships of older adolescents/young adults.

This study used self-report of older adolescent/young adult children from a general college population to examine if violent parental conflict tactics predict the use of similarly violent tactics in the same-sex and opposite-sex peer relationships of offspring. Conflict Tactics Scale date from 256 subjects indicate that parental violence within the marital dyad is predictive of violence in both same-sex and opposite-sex peer relationships. Surprisingly high frequencies of violence were reported within parents' marriages and by subjects in their current peer relationships. Implications of these findings are discussed.

Adolescent↗
PubMed1993

Feasibility of patient immobilization for conventional cranial irradiation with a relocatable stereotactic frame.

The precision of patient repositioning and the firmness of immobilization are among the major determinants of the accuracy of radiation treatment delivery. A relocatable Gill-Thomas localizer (GTL) developed for neurosurgery and stereotactic radiotherapy achieves highly accurate relocation and immobilization and has been used successfully for fractionated stereotactic radiotherapy of intracranial lesions. The feasibility of using GTL for immobilization in conventional fractionated external beam radiotherapy was assessed by comparison with conventional Cabulite shell head fixation. The GTL was well tolerated at the time of preparation and during a 5 week course of radiotherapy. The principal advantage was superior relocation accuracy maintained throughout the course of treatment, high precision of field set-up and markedly reduced production time. In addition the time taken to position the patient in the treatment room was also marginally shortened. GTL is therefore a feasible method of head fixation for conventional cranial irradiation providing patients have adequate dentition. With further development the relocatable method of immobilization originally designed for stereotactic radiotherapy may become the preferred technique particularly in situations where high accuracy is desirable, such as stereotactically guided conformal radiotherapy.

Adenoma↗
PubMed1991

A prospective evaluation of the Button gastrostomy in children.

The Button gastrostomy has become popular for patients requiring long-term enteral feeding, because it is considered less irritating, more stable and more esthetically acceptable than the traditional tube gastrostomy. By a standardized questionnaire and personal interview, the authors evaluated prospectively the efficacy and complication rate in 19 children who had a Button gastrostomy inserted during a 6-month period. In 15 children the Button replaced a standard tube gastrostomy, and in 4 the Button was inserted surgically initially. Thirteen children had severe neurologic disabilities, and 6 required supplemental enteral feeding as part of the nutritional management of another chronic disease. In all 19 children, the Button was esthetically more acceptable and produced less skin irritation than the standard tube gastrostomy. All but one caregiver thought that the Button gastrostomy was preferable to a tube gastrostomy. This was especially apparent in the six neurologically normal children who were able to be more active and had an improved self-image. Cost analysis showed that, despite the higher initial cost of the Button, elimination of the need for frequent tube changes and hospital visits made it ultimately more cost effective than the standard tube gastrostomy. The authors conclude that the Button gastrostomy is a useful alternative to the standard tube gastrostomy in selected patients. Close long-term follow-up is extremely important to ensure a good result.

Adolescent↗
PubMed1990

On the job.

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Humans↗