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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 181 records · Page 10Linked to original sources

Ewing's sarcoma and primitive neuroectodermal tumor in adults: are they different from Ewing's sarcoma and primitive neuroectodermal tumor in children?

PURPOSE: To determine whether age at diagnosis influences the behavior of Ewing's sarcoma and primitive neuroectodermal tumor (PNET). PATIENTS AND METHODS: We reviewed the clinical features, treatment, and outcome of 59 consecutive patients with Ewing's sarcoma and PNET treated on the Adult Sarcoma Unit at our institution from 1980 to 1995. RESULTS: The 37 male and 22 female patients had a median age of 24 years. Lower limb was the most common primary tumor site. Fifteen patients had nonmetastatic tumor less than 100-mL volume, 27 had nonmetastatic disease greater than 100-mL volume, and 17 had evidence of metastatic disease at presentation. The origin of the primary tumor was soft tissue in 28 cases, bone in 30, and uncertain in one. The Kaplan-Meier estimate of 5-year overall survival (OS) in all patients was 38% and of progression-free survival (PFS), 27%. When patients with metastatic disease at presentation were excluded, these figures increased to 52% and 34%, respectively. Bulk of disease at presentation and response to primary treatment were statistically highly significant predictors of both PFS and OS. Age and tissue of origin of the tumor did not influence outcome. CONCLUSION: The behavior of Ewing's sarcoma and PNET in adults is no different from its behavior in children. We feel the way forward in the treatment of adults with Ewing's sarcoma and PNET is for them to be included in the current multicenter trials of multidisciplinary treatment directed at children.

Adolescent↗

Abnormal carotid arterial wall dynamics in symptom-free hypopituitary adults.

OBJECTIVE: Although vascular mortality is increased in hypopituitary adults on routine replacement, there are limited data on the atherosclerotic process during life in these patients. Measurement of arterial stiffness may provide an index of early vascular changes that predispose to the development of major vascular accidents. DESIGN: Thirty-four hypopituitary adults on conventional replacement therapy and 39 age- and sex-matched controls were studied. They had no history or clinical evidence of macrovascular disease. The common carotid artery distensibility coefficient (DC), compliance coefficient (CC) and arterial stiffness index (beta index) were calculated from high-resolution ultrasonic imaging of the two common carotid arteries and from the brachial blood pressure. RESULTS: There was no difference between patients and controls in carotid diastolic diameter (mean +/- S.E.M) (5.55 +/- 0.16 vs 5.45 +/- 0.08 mm) and pulse pressure (6.66 +/- 0.30 vs 6.58 +/- 0.24 kPa). The increase in diameter during systole was significantly lower in the hypopituitary patients (0.39 +/- 0.02 vs 0.50 +/- 0.03 mm, P < 0.001). The DC was significantly lower in patients than in controls (24.2 +/- 2.29 vs 30.1 +/- 2.01 10(-3) kPa-1, P < 0.05). The carotid CC was also significantly lower in patients than in controls (5.7 +/- 0.49 vs 7.0 +/- 0.45 10(-7) m2 kPa-1, P < 0.05). The beta index was higher in the patient group (8.4 +/- 1.3 vs 5.9 +/- 0.37, P < 0.05). When men and women were considered separately, the differences between patients and controls were statistically significant in women but not in men and were more marked in the older women subgroup. CONCLUSIONS: Asymptomatic hypopituitary adults (especially women) on conventional replacement therapy have increased stiffness of the common carotid arteries. These findings provide additional evidence for a process leading to premature atherosclerosis in this group of patients.

Adult↗

Benchmarking in home care.

Recognizing that continuous quality improvement will be imperative for success in the future, six visiting nurse associations of northwestern Pennsylvania used benchmarking as a tool to improve their respective agencies' performance. The agencies benchmarked three areas: continuity of care, patient rehospitalization, and nosocomial infection rate.

Continuity of Patient Care↗

'I love my work.'.

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History, 20th Century↗

Endocrine disorders associated with inappropriately high aromatase expression.

Aromatase P450 (P450arom) is responsible for conversion of C19 steroids to estrogens in a number of human tissues, such as the placenta, gonads, adipose tissue, skin and the brain. Aromatase expression in human tissues is regulated by use of alternative promoters in the placenta (promoter I.1), adipose tissue (promoters I.4, I.3 and II) and gonads (promoter II). Aromatase expression is absent in the disease-free adult liver, adrenal and uterine tissues. Excessive or inappropriate aromatase expression in adipose fibroblasts and endometriosis-derived stromal cells, as well as in testicular, hepatic, adrenal and uterine tumors, is associated with abnormally high circulating estrogen levels and/or with increased local estrogen concentrations in these tissues. Whether systemically delivered or locally produced, elevated estrogen levels will in turn promote the growth of hormone-responsive tissues. We recently studied aromatase expression in testicular tumor and adipose tissue samples from prepubertal boys with gynecomastia, in hepatocellular cancer and adrenocortical tumor samples from adult men with gynecomastia, in breast adipose tissue samples proximal to breast tumors, and in endometrial cancer, leiomyoma and endometriosis tissues. Excessive aromatase activity and P450arom transcript levels were found in these tissue samples or in cultured cells derived from these tissues. In these neoplastic or non-neoplastic tissues or cells, the regulation of aromatase expression was studied in terms of alternative promoter use, both in vivo and in response to various hormonal stimuli. Our results were suggestive of a common metabolic abnormality associated with activation of a cyclic AMP-dependent signalling pathway that gives rise to transcriptional transactivation of aromatase expression via promoters I.3 and II in all of the above tissues. This article describes the common pathophysiological and molecular features of excessive aromatase expression in these disease states.

Adolescent↗

SFV topoisomerase: sequence specificity in a genetically mapped interval.

Poxviral DNA topoisomerases are sequence-specific enzymes whose activities are thought to influence such diverse processes as transcription, DNA replication, and genetic recombination. To obtain further insights into the relatedness of these enzymes, and their influence on virus-mediated recombination, we have determined the target-specificity and other catalytic properties of the Shope fibroma virus (SFV) topoisomerase. SFV topoisomerase was expressed in Escherichia coli and purified as a glutathione S-transferase (GST) or (his)6-tagged fusion protein. The recombinant Leporipox-virus (SFV) enzyme displayed catalytic properties very similar to vaccinia topoisomerase. In particular SFV topoisomerase recognizes the same pentanucleotide motif [5'-(C/T)CCTT-3'] and promotes the same DNA relaxation, strand transfer, and strand cleavage reactions catalyzed by the Orthopoxviral (vaccinia) enzyme. The SFV enzyme can also efficiently cleave DNA 3' of the variant site 5'-CCCTG-3' in certain sequence contexts. These studies identified several sites where SFV topoisomerases interact with a recombinational substrate and permitted a comparison of recombination frequencies across intervals which did, or did not, span these sites. We failed to detect any effect of topoisomerase-recognition sites on recombination frequencies, except for a small (< 2-fold) stimulation seen when the substrates encoded a nearby poxviral promoter. This and other work shows that poxviral topoisomerases from several genera share common target specificities, but other enzymatic systems probably catalyze the high-frequency recombination seen in poxvirus-infected cells.

Amino Acid Sequence↗

Inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis and DMBA-DNA adduct formation by curcumin.

Curcumin, a constituent of the traditional Indian spice and medicine turmeric, was evaluated for its capacity to inhibit the mammary tumor initiating activity of 7,12-dimethylbenz[a]anthracene (DMBA) and the in vivo formation of mammary DMBA-DNA adducts in the female rat. Administration (i.p.) of curcumin at 100 mg/kg and 200 mg/kg doses was associated with a significant decrease in the number of palpable mammary tumors and mammary adenocarcinomas. The in vivo formation of mammary DMBA-DNA adducts also was depressed for animals administered curcumin doses from 50 mg/kg to 200 mg/kg. There was, however, no significant enhancement of liver glutathione-S-transferase activity following curcumin administration. Therefore, curcumin when administered i.p. can act as an effective chemopreventative agent towards DMBA-induced rat mammary tumorigenesis and mammary adduct formation.

9,10-Dimethyl-1,2-benzanthracene↗