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Biomedical subjects

J A Scott

Publications and source records attributed to J A Scott.

At least 73 records · Page 4Linked to original sources
PubMed1998

Ischemic tolerance in skeletal muscle: role of nitric oxide.

We tested the hypothesis that ischemic preconditioning (PC) of skeletal muscle provided tolerance to a subsequent ischemic event 24 h later, and that such protection was due to nitric oxide (NO). Male Wistar rats, anesthetized with halothane, were randomly assigned to groups: ischemic (no PC; n = 11), PC (n = 11), PC + N-nitro-L-arginine methyl ester (L-NAME; 100 micromol/l; n = 5), PC + N-nitro-D-arginine methyl ester (100 micromol/l; n= 4), PC + aminoguanidine (AMG; 100 micromol/l; n = 4), ischemic + L-NAME (n= 4), or ischemic + AMG (n = 4). PC consisted of 5x 10 min of ischemia and reperfusion, and, 24 h later, 2 h of ischemia were induced by a tourniquet applied to the limb. With the use of intravital microscopy, the number of perfused capillaries (Npc) in the extensor digitorum longus (EDL) muscle was measured over a 90-min reperfusion period. The ratio of ethidium bromide- to bisbenzimide-labeled nuclei was used to estimate tissue injury. PC preserved Npc (23.6 +/- 2.5) following 2 h of ischemia compared with sham muscles (11.5 +/- 5.1), significantly elevating inducible NO synthase (iNOS) activity (81% increase), but did not afford protection to the parenchyma. L-NAME and AMG prevented ischemia-reperfusion-induced reduction in Npc in muscles without PC. However, after 90 min of reperfusion, L-NAME (Npc = 15.0 +/- 1.7), but not AMG (Npc = 22.8 +/- 3.1), significantly reduced the microvascular protection afforded by PC. We conclude that PC of the EDL muscle resulted, 24 h later, in protection to microvascular perfusion only, and that such protection was due to NO from sources other than iNOS.

Animals↗
PubMed1998

Osteopontin inhibits inducible nitric oxide synthase activity in rat vascular tissue.

We tested the hypothesis that osteopontin (OPN) can inhibit the induction of inducible nitric oxide synthase (iNOS) in vascular tissue. iNOS activity was induced in rat thoracic aortas by incubation of the tissue with lipopolysaccharide (LPS) and measured by conversion of L-[3H]arginine to L-[3H]citrulline. Addition of >/=1 nM recombinant OPN protein significantly reduced the LPS-induced increase in iNOS activity. Western blotting and the RT-PCR were used to determine the effect of LPS with and without OPN on tissue levels of iNOS protein and RNA, respectively. LPS resulted in an increase in iNOS protein and RNA, whereas OPN dose-dependently reduced tissue levels of iNOS activity, protein, and RNA. Mutated OPN proteins, in which the integrin-binding RGD amino acid sequence was deleted or mutated to RGE, resulted in complete and partial loss, respectively, of the ability of OPN to inhibit LPS-induced iNOS activity, implicating integrin binding in the effect. These results indicate that OPN can prevent induction of iNOS in vascular tissue.

Animals↗
PubMed1998

Role of intraoperative angiography in the surgical treatment of cerebral aneurysms.

UNLABELLED: The benefit of using intraoperative angiography (IA) during aneurysm surgery is still uncertain. OBJECT: In this prospective study, the authors evaluate the radiographically demonstrated success of surgical treatment in 151 consecutive patients harboring 173 aneurysms who selectively underwent IA examination. The authors also assess the frequency with which IA led to repositioning of the aneurysm clip. METHODS: Intraoperative angiography was used selectively in this series, based on the surgeon's concern about the potential for residual aneurysm, distal branch occlusion, or parent vessel stenosis. Specific variables were analyzed to determine their impact on the incidence of clip repositioning and the accuracy of IA was evaluated by direct comparison with postoperative angiography (PA) in 90% of the cases in which IA was used. CONCLUSIONS: The selective use of IA led to successful treatment as shown by PA, with a low incidence of unexpected residual aneurysm (3.2%), distal branch occlusion (1.9%), and parent vessel stenosis (0%). Intraoperative angiography led to immediate repositioning of the aneurysm clip in 27% of the cases. Anterior cerebral artery aneurysms required clip repositioning less often and superior hypophyseal artery aneurysms required repositioning more often than aneurysms in other locations. Large and giant aneurysms required clip repositioning more often than small aneurysms; however, they were also more likely to display false success on IA as determined by PA. Aneurysms arising along the internal carotid artery were more likely to display successful clipping on IA, as determined by PA, than were aneurysms in other locations. The results of this series support the selective use of IA in the treatment of complex aneurysms, particularly large and giant aneurysms as well as superior hypophyseal artery aneurysms. As measured by PA, IA will improve the outcome of these patients.

Adult↗
PubMed1997

Anserinones A and B: new antifungal and antibacterial benzoquinones from the coprophilous fungus Podospora anserina.

Two new benzoquinones with antifungal, antibacterial, and cytotoxic activities have been isolated from liquid cultures of the coprophilous fungus Podospora anserina. The structures of anserinones A (1) and B (2) were assigned on the basis of MS and NMR results, and the absolute stereochemistry of 2 was deduced by analysis of 1H-NMR data for its (R)- and (S)-2-phenylbutyryl ester derivatives.

Anti-Bacterial Agents↗
PubMed1997

The Oncormed approach to genetic testing.

This report describes a commercial laboratory's novel approach to providing genetic testing services to detect BRCA1 mutations in persons with hereditary breast/ovarian cancer. The approach involves the use of institutional review board (IRB)-approved protocols as a paradigm for conducting genetic testing in a commercial setting. We discuss the rationale for this approach and the key elements of the protocol. In addition, we provide data on the first 6 months of implementation of the protocol in 32 clinical sites. A phased testing approach was used, consisting of an allele-specific oligonucleotide assay for the 8 most common BRCA1 mutations, a protein truncation test of exon 11, and direct sequencing of the remaining regions of the gene. Data are presented on the yield of mutation carriers by category of family history and by stage of analysis.

BRCA2 Protein↗
PubMed1997

Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells.

The efficacy of dietary selenium supplementation is currently being evaluated in intervention trials. However, the biological mechanisms underlying the cancer chemopreventive effects of selenium supplementation have yet to be elucidated. Selenium metabolism and polyamine biosynthesis are linked in their common requirement for S-adenosylmethionine. Selenomethionine was the predominant form of selenium in the dietary supplement, therefore we evaluated the anti-tumorigenic effects of selenomethionine. We found that selenomethionine inhibited tumor growth (both in A549 lung and HT29 colon cancer cells) in a dose-dependent manner. At 24 and 72 h, polyamine content of A549 and HT29 cancer cell lines was decreased at doses that inhibited 50% of normal growth. Selenomethionine treatment induced apoptosis in both cancer cell lines. Exogenous spermine administration, which replenishes intracellular polyamine levels, prevented selenomethionine induced apoptosis. Selenomethionine administration to the cancer cell lines increased the number of cells in metaphase. This cell cycle effect appeared to be reversed with the co-administration of selenomethionine and spermine. These data suggested that at least part of the anti-carcinogenic effects of selenium supplementation might be due to a depletion in polyamine levels. This depletion of polyamines leads to an induction in apoptosis and perturbations in the cell cycle.

Antineoplastic Agents↗
PubMed1997

The influence of reported paternal attitudes on the decision to breast-feed.

OBJECTIVE: To identify factors that influence a woman's decision to breast-feed. METHODOLOGY: Five hundred and fifty-six women were recruited from the maternity wards of two Perth hospitals. Data were collected from a self-administered questionnaire completed by participants prior to discharge. Logistic regression analysis was used to determine factors influencing the initiation of breast-feeding. RESULTS: At discharge from hospital 83.8% of women were breast-feeding, including 6% who were giving complementary formula feeds. After controlling for potentially confounding demographic and biomedical factors, the father's reported preference for breast-feeding was found to be the most important factor influencing a woman's decision to breast-feed (OR 10.18). CONCLUSION: Fathers participate in and influence the choice of infant feeding method and should be included in breast-feeding discussions.

Adult↗
PubMed1997

Histopathology and molecular cytogenetics of a corneal opacity associated with the trisomy 8 mosaic syndrome (46,XY/47,XY, +8).

The trisomy 8 mosaic syndrome (Tr8MS), karyotype 46,XY/47,XY, +8, is a rare multisystem disorder that may be associated with corneal opacity. We report the case of a dysmorphic infant with multiple congenital abnormalities referred to our unit with a congenital corneal opacity. Subsequent chromosomal analysis of peripheral leucocytes demonstrated constitutional Tr8MS. At 4 years of age, lamellar keratoplasty was performed. Histological examination confirmed the lesion to be consistent with a corneal choristoma. Cytogenetic studies using in situ hybridisation techniques showed the presence of trisomic cells in cell culture derived from the tissue in higher proportion (92%) than in the blood (44%). Amplification of the c-myc oncogene on chromosome-8 could not be detected in cells cultured from the corneal lesion. Although not proof, these findings lend support to the concept of the corneal lesion representing a focus of viable trisomic cells rather than an inflammatory response to a nidus of effete cells.

Abnormalities, Multiple↗
PubMed1996

Cercophorins A-C: novel antifungal and cytotoxic metabolites from the coprophilous fungus Cercophora areolata.

Cercophorins A-C (3-5), three novel isocoumarin derivatives with antifungal and cytotoxic activities, have been isolated from the coprophilous fungus Cercophora areolata (JS 166 = UAMH 7495), a colonist of porcupine dung. Two additional new isocoumarins, decarboxy-citrinone (1) and 4-acetyl-8-hydroxy-6-methoxy-5-methylisocoumarin (2), and a known tricothecene mycotoxin, roridin E (6), were also obtained from this species. Compounds 1-6 were isolated from ethyl acetate extracts of mycelia and liquid cultures of C. areolata through bioassay-guided fractionation and are the first metabolites to be reported from a member of the genus Cercophora. Their structures were assigned on the basis of MS, selective INEPT, and 2D-NMR experiments.

Antifungal Agents↗
PubMed1996

Serogroup-specific epidemiology of Streptococcus pneumoniae: associations with age, sex, and geography in 7,000 episodes of invasive disease.

A study sample of 7,010 episodes of invasive Streptococcus pneumoniae disease was obtained by combining 13 existing datasets. Disease episodes due to each of 12 pneumococcal serogroups (1, 3-9, 14, 18, 19, and 23) were then compared with episodes in a constant internal control group to describe serogroup-specific variations in disease frequency by age, sex, and geographic origin. The results are presented as odds ratios (with 95% confidence intervals) derived by logistic regression, with adjustment for the major confounders, including dataset of origin. Variation in the male:female ratios between serogroups is small, suggesting that capsular characteristics are an unlikely explanation for the male preference of S. pneumoniae. Serogroups associated with higher nasopharyngeal prevalence (e.g., 19 and 24) are relatively more common in Europe and North American, while the invasive serotypes 1 and 5 are much more common in South America. The custom of reporting serogroup frequencies in two age groups, children and adults, conceals much of the variation in the age distributions across the whole span of life. The reduction of risk associated with serogroups 6, 14, 18, 19, and 23 beyond childhood follows different gradients, being most abrupt in serogroups 14 and most gradual in serogroup 18. The relative risk of disease with serotype 1 declines steadily throughout life, while with serotypes 3 and 8 it increases over middle age. Serogroups 7 and 23 are found unusually frequently in the third decade of life. Because of the wide differences in the epidemiology of individual serogroups of S. pneumoniae, it is questionable whether pneumococcal infection should continue to be classified as a single disease entity.

Adolescent↗
PubMed1996

Impact of fluorodeoxyglucose positron emission tomography on the clinical management of patients with glioma.

The past decade has seen the identification of many clinical settings in the treatment of primary brain tumors in which information from fluorodeoxyglucose positron emission tomography (FDG-PET) might be useful, if not essential, to therapeutic formulation. FDG-PET is currently used at referral centers in the management of primary brain tumors. The clinical pattern of FDG-PET use was assessed and its value compared to other information sources in clinical decision making. The clinical records of 75 glioma patients who were evaluated by FDG-PET were reviewed. The range of circumstances in which FDG-PET was employed included: pretherapeutic baseline studies for monitoring the effect of a therapy (1% of all cases), mapping of hypermetabolic regions before surgery or biopsy (2%), mapping of hypermetabolic regions before radiotherapy (2%), postsurgical evaluation for residual tumor (2%), assessment of the malignancy of a mass as a substitute for biopsy (11%), and distinguishing between radiation necrosis and recurrent tumor (87%). Other sources of information that contributed to the therapeutic management of patients included: gadolinium-enhanced MRI, contrast-CT, and clinical findings.

Brain↗
PubMed1996

Breast-feeding in Perth: recent trends.

Analysis of breast-feeding data from the 1989-90 National Health Survey suggests that since peaking in the mid-1980s, breast-feeding initiation and duration rates have declined in Australia. Data from a recent prospective study of infant feeding practices among 556 women indicates that in Perth, at least, breast-feeding rates have remained relatively stable for the past nine years.

Breast Feeding↗
PubMed1996

Neural networks in ventilation-perfusion imaging.

PURPOSE: To optimize the performance of artificial neural networks in the prediction of pulmonary embolism from ventilation-perfusion (V-P) scans. MATERIALS AND METHODS: Neural networks were constructed with a set of V-P scan criteria that included sharpness and completeness of perfusion defects and involved quantification of abnormalities by using a continuous numeric scale. Several network parameters were systematically varied. Networks were trained with 150 cases and tested with 30 different cases. Findings were compared with those of pulmonary angiography. RESULTS: Networks capable of performing as well as experienced nuclear medicine physicians could be constructed with few V-P scan features. A brief training period was optimal (50-100 iterations). Further training diminished network performance. CONCLUSION: Effective neural networks can be constructed by using a limited number of unconventional V-P scan features. Several parameters can be adjusted to optimize performance.

Adolescent↗
PubMed1996

Neural networks in ventilation-perfusion imaging. Part II. Effects of interpretive variability.

PURPOSE: To evaluate the usefulness of a neural network developed by one physician and used by another. MATERIALS AND METHODS: Intra- and interobserver variability were analyzed in image categorization of ventilation-perfusion (V-P) scans. This information was used to estimate network performance when it was used by a physician who did not train the network. RESULTS: Network training was optimized by using input parameters that demonstrated both individually high correlations with pulmonary embolism and good reproducibility in multiple interpretations. CONCLUSION: Potential variability exists in the performance of a network when it is supplied with input data by different physicians. The clinical usefulness of a network depends heavily on the similarity of interpretive styles between the network trainer and the user.

Humans↗