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Biomedical subjects

G Scott

Publications and source records attributed to G Scott.

At least 127 records · Page 7Linked to original sources
PubMed1997

The molecular epidemiology of human immunodeficiency virus type 1 in six cities in Britain and Ireland.

We have sequenced the p17 coding regions of the gag gene from 211 patients infected either through injecting drug use (IDU) or by sexual intercourse between men from six cities in Scotland, N. England, N. Ireland, and the Republic of Ireland. All sequences were of subtype B. Phylogenetic analysis revealed substantial heterogeneity in the sequences from homosexual men. In contrast, sequence from over 80% of IDUs formed a relatively tight cluster, distinct both from those of published isolates and of the gay men. There was no large-scale clustering of sequences by city in either risk group, although a number of close associations between pairs of individuals were observed. From the known date of the HIV-1 epidemic among IDUs in Edinburgh, the rate of sequence divergence at synonymous sites is estimated to be about 0.8%. On this basis we estimate the date of divergence of the sequences among homosexual men to be about 1975, which may correspond to the origin of the B subtype epidemic.

Acquired Immunodeficiency Syndrome↗
PubMed1997

LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant fibrous histiocytoma.

BACKGROUND: In this study, the authors examined the expression of LN-2, an antigen expressed by B cells, macrophages, and Reed-Sternberg cells, in a variety of spindle cell lesions of the skin to determine whether LN-2 immunoreactivity can be used to differentiate among these tumors. For comparison, they examined CD34 antigen expression in these lesions, which has been shown to be a useful marker in differentiating dermatofibrosarcoma protuberans from dermatofibroma. METHODS: Immunocytochemistry with anti-LN-2 and anti-CD34 monoclonal antibodies on formalin fixed, paraffin embedded material was performed on 102 spindle cell lesions, including dermatofibroma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, malignant fibrous histiocytoma, leiomyoma, and neurofibroma. RESULTS: LN-2 immunoreactivity did not distinguish between dermatofibroma and dermatofibrosarcoma protuberans, both of which showed weak immunoreactivity. In marked contrast, 90% of cases of malignant fibrous histiocytoma showed strong staining for LN-2, whereas the vast majority (90%) of cases of atypical fibroxanthoma were negative or stained only weakly with anti-LN-2 antibodies. Of the two cases of atypical fibroxanthoma that stained strongly for LN-2, both lesions were > 2 cm in size and extended deep into the subcutaneous fat. CONCLUSIONS: Differential expression of the LN-2 antigen by atypical fibroxanthoma and malignant fibrous histiocytoma distinguishes these two lesions and suggests that acquisition of LN-2 positivity may be a marker of tumor progression.

Antibodies, Monoclonal↗
PubMed1997

Inactivation of recombinant monocyte cAMP-specific phosphodiesterase by cAMP analog, 8-[(4-bromo-2,3-dioxobutyl)thio]adenosine 3',5'-cyclic monophosphate.

Two cAMP analogs, 8- and 2- [(4-bromo-2,3-dioxobutyl)thio]adenosine 3',5'-cyclic monophosphate (8- and 2-BDB-TcAMP) have been used in probing the catalytic site of recombinant monocyte cAMP-specific phosphodiesterase (PDE4a). 2-BDB-TcAMP is a reversible and competitive inhibitor (Ki = 5.5 mumol/L) of cAMP hydrolysis by PDE4a, 8-BDB-TcAMP irreversibly inactivates the enzyme in a time- and concentration-dependent manner with a second order rate constant of 0.022 mmol/L-1 min-1. The rate of inactivation of PDE4a is reduced by the presence of the substrate cAMP and specific inhibitors, rolipram and denbufylline, but not by cGMP or AMP. Reduction of the enzyme-inhibitor complex with sodium [3H]borohydride shows that 1.2 mol of the affinity label/mol of enzyme was incorporated. The radiolabeled peptide is composed of 10 amino acid residues (697 to 706) located near the carboxyl end of the proposed catalytic domain. The peptide (GPGHPPLPDK) has seven nonpolar and aliphatic residues, of which four are proline, giving the peptide a highly structured conformation. This peptide is the first to be identified in the putative catalytic domain involved in substrate recognition.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Bone scintigraphic appearance of asymptomatic hydroxyapatite-coated hip arthroplasties.

To obtain information about the bone scintigraphic appearance of a hydroxyapatite (HA)-coated proximal femoral implant, this examination was performed on 24 patients with a clinically and radiologically successful femoral implant in hip arthroplasty. The prosthesis had a proximal HA coating for supplementary fixation. The patients' mean age was 50.3 years (range, 28-65 years) at operation. The interval from the operation to the scintigraphy ranged from 6 months to 5.5 years (mean, 2.2 years). Scintigraphy was performed using 99mTc-medronic acid. Quantitative counts were recorded in 4 zones: 3 along the length of the implant (trochanteric region with HA coating, midprosthesis, and distal tip) and 1 below the prosthesis. The results were expressed as ratios using the nonoperated femur as a control value. The results demonstrated that the mean activities in all 4 zones were increased relative to the untreated side. The highest activity was observed in the region around the prosthetic tip, with an elevation of 46% above the control value. This activity showed a significant decline over time. The counts recorded in the trochanteric region, where the implant was coated with HA, were 20% above the control value and similar to those seen in its adjacent noncoated midprosthetic region. In the trochanteric region, however, the activity did not show a decline over the follow-up period.

Adult↗
PubMed1997

Metabolism of a bisphosphonate ester (PNU-91638) in rat.

1. Metabolites of the cyclic bisphosphonate ester, 4-[2,2'-bis-(5,5- dimethyl-1,3,2-dioxaphosphorinan-2-yl)] butanoyl-3-fluoro-benzene (PNU-91638) in bile or urine of the male Sprague-Dawley rat were characterized by mass spectrometry. The chronically bile duct/duodenal-cannulated male rats received a single oral dose of 100 mg/kg [13C] [14C]PNU-91638. Bile and urine samples were analysed for radioactivity and profiled by hplc with radiometric and UV detection. 2. The 0-28-h bile and urine accounted for 46.0 and 19.7% of dose respectively. The structures of radioactive peaks were investigated by ionspray and liquid secondary ion mass spectrometry (LSIMS) and LSIMS/MS analysis. 3. Major metabolites in urine included two regioisomeric phenol glucuronides, a gem methyl hydroxylated metabolite of the bisphosphonate heterocycle, a phenol metabolite, parent drug and a benzylic alcohol metabolite. Additional metabolites in bile included an unstable phenol/glutathione adduct (from a putative epoxide intermediate) with several minor isobaric regioisomers, and a carboxylic acid derived from the gem methyl hydroxylated bisphosphonate ring. 4. The structures proposed have not been confirmed by nmr due to discontinuation of the development of PNU-91638.

Animals↗
PubMed1997

Axonal injury in falls.

Amyloid precursor protein (APP) immunocytochemistry was used as a marker for axonal injury (AI) in a series of 16 cases of head trauma associated with fatal falls. Nine cases were falls from not more than the person's own height (falls from < or = own height) and seven cases were falls from a distance greater than the person's own height (falls from > own height). AI was recorded on a series of line diagrams of standard brain sections divided into 116 sectors. AI around focal lesions (infarcts, hemorrhages, contusions) was distinguished from nonfocal axonal injury that was distant from any focal area of damage. The percentage of sectors showing focal AI provided the Focal Axonal Injury Score (FAIS) and the percentage showing nonfocal AI the Non-Focal Axonal Injury Score (NFAIS). The FAIS is a measure of secondary AI and the NFAIS of diffuse axonal injury (DAI). The percentage of sectors involved with AI (focal and nonfocal) provided the cumulative Axonal Injury Score (AIS). A semiquantitative grading system was also used to assess the severity of axonal injury in each sector and the sum of the grades from all sectors was expressed as a percentage to provide the Axonal Injury Severity Score (AISS). Widespread AI was present in all cases irrespective of the height of the fall. AI was present in the midbrain (94%), pons (94%), corpus callosum (100%), central grey matter (100%), and cerebral hemispheric white matter (94%). AIS ranged from 10 to 94 in falls from < or = own height (mean 73) and from 38 to 92 in falls from > own height (mean 82). AISS ranged from 6 to 95 in falls from < or = own height (mean 65) and 28 to 95 in falls from > own height (mean 72). There was no statistically significant difference in AIS or AISS between the two groups. The extent and severity of AI cannot be predicted from biomechanical data, such as the height of the fall, as the total AI in a given case is a variable mixture of Nonfocal AI (DAI) and Focal AI arising by secondary mechanisms, and APP immunostaining is unable to distinguish primary from secondary AI. However, the combination of the Hypoxic-Ischemic Score (HIS) defined as the percentage of sectors showing any hypoxic-ischemic damage ranging from neuronal "red cell change" to infarction in conjunction with the FAIS and NFAIS provided a measure of the relative contribution of primary and secondary AI in a given brain.

Accidental Falls↗
PubMed1997

Simple identification of dominant p53 mutants by a yeast functional assay.

Analysis of families with germline p53 mutations shows that the mutant p53 allele behaves as a dominant oncogene at the genetic level, although it behaves as a recessive oncogene at the cellular level, since tumours invariably show mutation or loss of both wild-type alleles. At the biochemical level it is possible that some clinically important mutant p53 proteins may be carcinogenic through a dominant mechanism. We show that p53 mutants can be readily classified according to their dominant potential using a simple yeast functional assay. Wild-type p53 is constitutively expressed from a TRP1 vector, p53 mutants are expressed from an otherwise identical LEU2 vector and net transcriptional activity is scored using an ADE2-based reporter. Twenty seven p53 mutants were tested: 19 were recessive, i.e. gave white colonies, and eight showed dominant activity, i.e. gave pink/red colonies. This simple assay should facilitate studies on p53 dominance.

DNA, Complementary↗
PubMed1997

Wear particulate species and bone loss in failed total joint arthroplasties.

The aim of this study was to evaluate the relative contribution of polyethylene, metal, and polymethylmethacrylate (cement) particles to the overall bone loss in aseptic loosening. Twenty-four interface tissues with adjacent bone were obtained during 17 revision total joint arthroplasties (11 hips and six knees). Osteoclasts and macrophages were identified immunohistochemically on the bone surface. The length of the bone surface in contact with these cell types was measured and analyzed with reference to the particulate species present within the fibrous interface. The presence of abundant polyethylene particles significantly increased the proportion of the bone surface in contact with macrophages but did not have a significant influence on that of osteoclasts. Osteoclastic bone resorption was significantly more extensive in the presence of metal particles. In contrast, the presence of cement particles did not have a significant influence on macrophage or osteoclast coverage of the bone surface. These results highlight the significance of polyethylene particles in macrophage recruitment and subsequent osteolysis and suggest a different mechanism of bone loss related to metal, namely mediation through osteoclastic activities. The relative contribution of cement particles was negligible and needs reevaluation in light of evidence provided by others.

Adult↗
PubMed1997

Topical application of viral vectors for epidermal gene transfer.

Efficient gene transfer with extended gene expression is essential for successful treatment of skin diseases using gene therapy. Previously we evaluated a physical gene transfer method (gene gun delivery) for its ability to transfect the epidermis in vivo. In this study, we tested two viral vectors for their ability to transduce murine epidermis through topical application. Both an adenoviral vector and a herpes simplex virus (HSV) amplicon vector transduced murine epidermis with high efficiency after topical application. Differences in amount and duration of transgene expression were compared between these two vectors. Quantitative analysis of reporter lacZ gene expression showed that the viral vector-mediated gene transfers were superior to gene-gun delivery of plasmid DNA. Significant necrosis and cytotoxicity, however, were observed in the HSV-treated skin. In addition, we show that murine epidermis developed hyperkeratosis and acanthosis 4 d after an adenoviral vector containing a human TGF-alpha expression unit was applied topically. Finally we demonstrate the feasibility of transduction of fetal skin in utero by intraamniotic injection of an adenovirus vector.

Acanthosis Nigricans↗
PubMed1997

Fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent mechanism.

Recent reports show that components of the extracellular matrix function as cell survival factors through the suppression of apoptosis (programmed cell death). In this report we show that attachment to fibronectin suppresses apoptosis of normal human fetal and neonatal melanocytes in vitro and that prevention of attachment to underlying matrix or attachment to poly-L-lysine is a potent inducer of apoptosis in melanocytes. A role for the beta1-integrin family in mediating cell survival signals was shown by the ability of beta1-blocking antibodies to enhance apoptosis in melanocytes attached to fibronectin, and by the ability of anti-beta1 antibodies immobilized on solid supports to suppress apoptosis in melanocytes. Cytochalasin D reversed the effect of fibronectin on the suppression of apoptosis in melanocytes, suggesting that an intact cytoskeleton is required for transduction of survival signals. A human metastatic melanoma cell line, SKMEL28, was resistant to apoptosis when grown in suspension or on poly-L-lysine, even after 4 d in culture in the absence of exogenous growth factors. These results suggest that fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent pathway and that significant differences in the control of anchorage-dependent regulation of apoptosis exist in melanocytes and melanoma cells.

Antibodies↗