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Biomedical subjects

D Cross

Publications and source records attributed to D Cross.

At least 55 records · Page 3Linked to original sources

Prognostic value of p53 overexpression and c-Ki-ras gene mutations in colorectal cancer.

BACKGROUND: Mutations in Ki-ras codon 12 and the p53 gene are common abnormalities in colorectal cancer. The occurrence of p53 overexpression and/or Ki-ras codon 12 mutations were analyzed in 100 colorectal adenomas to determine if they were related to patient survival. METHODS: p53 overexpression was identified by immunohistochemistry, and Ki-ras codon 12 mutations were detected using the polymerase chain reaction and a restriction enzyme digestion method. RESULTS: p53 overexpression was identified in 45% of tumors, with a higher frequency identified in DNA aneuploid and left-sided tumors than in DNA diploid and right-sided tumors. Mutations in Ki-ras codon 12 were identified in 24% of carcinomas. Individually, mutations in Ki-ras codon 12 or p53 overexpression were not prognostic indicators of survival. However, a statistically significant difference in survival was identified when these two oncogenic abnormalities were analyzed together. The median survival of patients whose tumors contained both oncogenic abnormalities was less than half of that of patients with either alteration alone or without either abnormality. CONCLUSIONS: Screening for multiple genetic abnormalities in colorectal cancers excised at surgery may prove to be a useful tool in determining prognosis.

Adenocarcinoma↗

Flow cytometry and AgNORs in benign, borderline, and malignant mucinous and serous tumours of the ovary.

We performed flow cytometry and AgNOR counts on 117 serous and mucinous ovarian tumours, comprising 56 cystadenomas, 21 borderline tumours, and 40 cystadenocarcinomas. DNA aneuploidy was present in one cystadenoma and in 11% of mucinous and 46% of serous cystadenocarcinomas. All borderline tumours were DNA diploid. Major and minor FIGO stages and flow cytometrically determined DNA ploidy and DNA index were prognostically significant. Age, histological type (serous versus mucinous), flow cytometric proliferative index, and AgNOR counts were not predictive of survival. Cystadenomas and borderline tumours had lower rates of proliferation than cystadenocarcinomas. AgNORs correlated with DNA ploidy and proliferative index. Borderline tumours showed elevated AgNOR numbers despite low proliferative indices and universal DNA diploidy, suggesting that AgNOR numbers may be related to nuclear events other than proliferation and DNA ploidy.

Adult↗

Repeat thrombolysis.

Since 20% of patients with myocardial infarction (MI) have had a previous infarction, and reinfarction within one year after infarction occurs in 9% of cases, it is important to clarify the role of repeat thrombolysis. After streptokinase (SK) administration, IgG antibodies rise to a peak at two weeks and slowly fall over the next 12 months, but 50% of patients still have antibody levels sufficient to neutralise a standard dose of SK up to four years after initial SK administration. On this evidence, SK or anistreplase should not be readministered, except perhaps in the first two to three days after initial treatment. The efficacy of tissue plasminogen activator (t-PA) and urokinase is not affected by prior treatment with SK.

Antibodies↗

Ten unanswered questions regarding comprehensive school health promotion.

The past two decades witnessed dramatic growth in support for comprehensive school health promotion. Yet, many questions about its effectiveness and feasibility remain unanswered. This article poses several research and policy questions, the answers to which may help to shape the future of school health programs in this country.

Adolescent↗

A tau-like protein interacts with stress fibers and microtubules in human and rodent cultured cell lines.

The cytoskeletal integrity of human and rodent cell lines was analyzed using site-directed monoclonal antibodies prepared from hybridomas. Secreting hybridomas were produced by immunizing mice with synthetic peptides from the C-terminal domain of the beta II-tubulin isotype, beta II(422-434), YQQYQDATADEQG, and the first imperfect repeat from brain tau, Tau-I(187-204), VRSKIGSTENLKHQPGGG. Two hybridomas were selected for this work: MTB6.22, an anti-idiotypic monoclonal antibody, which was obtained from a mouse immunized with the beta II-peptide and recognizes specific tubulin-binding domains on MAP-2 and tau; and Tau-I/1, which recognizes the repetitive binding sequences on tau and MAP-2. Immunoblots of cytoskeletal protein preparations from the five different tumor cell lines studied, showed the interaction of the site-directed antibodies MTB6.22 and Tau-I/1 with a group of proteins that co-migrate with brain tau. Immunoreactive tau components were also identified using an anti-tau monoclonal antibody (clone Tau-2), and several polyclonal anti-tau antibodies that interact with tau epitopes, other than those of the tubulin-binding domains. These tau-like proteins bound to a calmodulin-Sepharose affinity column and were eluted using 2 mM EGTA. Interestingly, washing the extracted cytoskeleton pellet with 5 x 10(-3) M Ca2+ for short periods of time selectively released the tau-like protein components, whilst most of the other cytoskeletal proteins remained in the pellet. On the other hand, immunofluorescence microscopy of detergent-extracted cells showed immunostaining of MAP components that appear to be co-localized in a discrete dot-like distribution along the stress fibers, which were revealed using rhodamine-phallacidin. Further support for the specificity of tau interaction with sites on tubulin and actin polymers was obtained with double-immunofluorescence, using the MAP-reactive monoclonal antibody MTB6.22 and a polyclonal antibody to a tubulin peptide containing part of the tau-binding domain on tubulin. Considering the anti-idiotypic nature of the MTB6.22 monoclonal antibody, our studies indicate that, in all the cell lines analyzed, a tau-like protein component is involved in mediating the interaction of both actin and tubulin polymers.

Actins↗

The Know Your Body program: a review of evaluation studies.

Know Your Body is a comprehensive school health promotion program for kindergarten through six grades, initially developed in the 1970s by the American Health Foundation. The impact of the KYB program has been evaluated in three field trials, the results of which have been reviewed in this article. Across the three studies, at 3-year follow-up, consistent positive intervention effects were reported for systolic blood pressure, diastolic blood pressure, smoking, HDL-cholesterol, and health knowledge. Results for total blood cholesterol, fitness score, heart-healthy snacks, fruit/vegetable intake, whole milk intake, and health attitudes were mixed. For body mass index, triceps skinfold, all remaining dietary variables, self-esteem/self-efficacy, and locus of control no significant effects were observed. Overall, significant treatment effects were reported for 19 of the 40 variables assessed at 3-year follow-up, an effects ratio of 48%. Consistent positive results at 5-year follow-up were reported for smoking and health knowledge. Mixed results were obtained for total blood cholesterol, diastolic blood pressure, and percent kilocalories from saturated fat. Consistent null results were reported for HDL-cholesterol, systolic blood pressure, body mass index, triceps skinfold, fitness score, percentage kilocalories from fat, cholesterol intake, and fiber intake. Overall, significant treatment effects were reported for 7 of 36 variables at 5-year follow-up, an effects ratio of 19%. Although reported program effects were largely mixed, they seem consistent with other health education evaluations. Null results may have been related to insufficient teacher implementation as well as weaknesses in design and assessment. Additional research is needed to determine the effect of the program on a broader range of outcomes, to what degree increasing the "dose" produces larger and more enduring treatment effects, and the relative impact of the various components that comprise the program.

Child↗

Are parents' self-reported total cholesterol levels useful in identifying children with hyperlipidemia? An examination of current guidelines.

OBJECTIVE: Recently, the American Academy of Pediatrics (AAP) Committee on Nutrition adopted the recommendation of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (NCEP) that children and adolescents with a family history of premature cardiovascular disease or parental hypercholesterolemia (> or = 240 mg/dL) be screened for hyperlipidemia. The rationale for using parental hypercholesterolemia as a screening trigger is based on sensitivity estimates using parents' actual lipid values. However, in clinical practice pediatricians may often have to rely on parents' self-reported cholesterol levels to determine a child's family risk history. This study examines the feasibility and utility of parental self-reported cholesterol levels as a means of identifying children with elevated total cholesterol levels. METHODS: As part of a school-based risk factor screening program that included total cholesterol measurement, conducted in nine elementary schools between 1989 and 1991, parents of participating children were asked if they had their cholesterol tested in the past year and if they had, to provide their total cholesterol values. RESULTS: If only the children who had one parent with a self-reported total cholesterol value > or = 240 mg/dL would have been screened, between 90% and 93% of children with elevated total cholesterol values, either > or = 170 mg/dL or > or = 200 mg/dL, would have been missed. CONCLUSIONS: These data suggest that parents' self-reported cholesterol values are an ineffective means of identifying children with elevated total cholesterol and modification of the current AAP, and NCEP guidelines for selective cholesterol screening in children may be warranted.

Adult↗

The right-hemisphere bias in conditional reasoning: a short report on multiple failures to replicate previous findings.

The present set of studies attempted to replicate Gellatly's (1985) findings that were supportive of Evan's (1982) hypothesis that the right hemisphere produces a selective bias towards the incorrect solution of a complex reasoning task. Subjects solved problems of the form "if p then q." In four studies, participants simultaneously performed a bottle--balancing task on each hand to interfere with processing of the reasoning task in the right hemisphere. In the fifth study, the bottle--balancing task was replaced by a finger--sequencing task. The results of the five studies did not show that the interference with right-hemisphere activity resulted in better performance on the conditional-reasoning task. It is concluded that the hypothesis of a right-hemisphere bias in conditional reasoning is still in need of reliable findings.

Attention↗

An interpersonal-epistemological curriculum model for nurse education.

This paper proposes a curriculum model for nurse education which holds forms of knowledge and interpersonal relationships as key issues if nurse education is to develop autonomous, reflective, critical practitioners. By adopting areas of cognitive interest, principles of andragogy and the concept of reflection-in-action, the model provides a heuristic tool which attempts to enable the provision of a nurse education which is devoted to adult learning processes and relevant to the development of education in the practice setting. The technical, practical and emancipatory areas of cognitive interest provide an understanding of learning domains which require different knowledge bases, methods of learning and forms of assessment to each other. The pedagogy/andragogy dichotomy is presented to reflect two teaching paradigms. The former approach is derived from the activity of teaching children and provides for passive dependence. The latter is more appropriate to adult learning and student self-direction. The model attempts to promote the transitional dynamic which moves the student nurse toward a state of greater self-direction. Finally, the concept of reflection-in-action is discussed in an attempt to ensure that the areas of cognitive interest and the learning strategies are inextricably linked to the practice component of a professional nurse education. All three dimensions are combined to show how each should develop in unison as the professional education of the nurse proceeds along a chronological dimension.

Clinical Competence↗

A three-year evaluation of the know your body program in inner-city schoolchildren.

The impact of the Know Your Body (KYB) comprehensive school health education program was evaluated in a sample of first through sixth-grade students from New York City, using two analytic strategies: a longitudinal cohort and a "posttest only" cohort. In both cohorts, program impact was examined between condition (i.e., KYB vs. no-treatment comparison group) as well as within condition (i.e., low, moderate, and high student exposure). Students in the longitudinal cohort (n = 1,209) who were exposed to high implementation teachers had significantly (p < .05) lower total plasma cholesterol and systolic blood pressure at 3-year posttest than comparison students. Students in the posttest only cohort (n = 3,066) who had high implementation teachers showed significantly (p < .05) lower total plasma cholesterol, systolic blood pressure, self-reported intake of meat and desserts, as well as higher health knowledge and self-reported intake of "heart healthy" foods and vegetables than comparison students. In both cohorts, program effects for several outcome variables were linearly related to level of student exposure to the curriculum, suggesting a dose-response effect. While several methodologic limitations may have influenced study outcomes, these data nonetheless appear to confirm that the KYB program can have a significant positive impact on the knowledge, behavior, and selected risk factors of students in primary grades and that efforts to disseminate and evaluate school health education programs should include strategies to monitor and enhance teacher implementation.

Blood Pressure↗

Comparison of effects of thrombolytic therapy on left ventricular function in patients over with those under 60 years of age.

This study examined the effect of age on left ventricular (LV) function, assessed by contrast ventriculography 3 weeks after a first acute myocardial infarction in 312 patients who received thrombolytic therapy within 4 hours of the onset of infarction and in 83 patients who received placebo. Streptokinase was given to 188 patients and recombinant tissue-type plasminogen activator (rt-PA) to 124. Patients were divided into 2 age groups: less than 60 years (n = 244) and greater than or equal to 60 years (n = 151). Thrombolytic therapy improved ejection fraction in both age groups: from 54 +/- 13 to 59 +/- 11% (p = 0.021) in the younger group and from 50 +/- 14 to 57 +/- 13% (p = 0.004) in the older group. Ejection fraction was identical in streptokinase- and rt-PA-treated patients. Multifactor analysis of variance revealed that younger age and thrombolytic therapy were independently associated with improved ejection fraction. Thrombolytic therapy also reduced end-systolic volume (p = 0.001) by 14 ml in the elderly and 9 ml in the younger group. Minor bleeding complications were more frequent in the elderly and 3 serious hemorrhages occurred in patients greater than or equal to 60 years. These findings reveal that thrombolysis improves LV function in all age groups studied. Because increasing age is independently associated with a lower ejection fraction after acute myocardial infarction, thrombolytic therapy may confer greater benefits in older patients.

Age Factors↗

MAP-1 and MAP-2 binding sites at the C-terminus of beta-tubulin. Studies with synthetic tubulin peptides.

The interaction of microtubule-associated proteins MAP-1 and MAP-2 with different peptides containing sequences covering the C-terminal region of beta-tubulin isoforms has been analyzed. Our results indicate that MAP-1 and MAP-2 bind to a common sequence within the variable C-terminal region of the different beta-tubulin isoforms, while MAP-2 also interacts with the subdomain beta (422-434) of the constant region, in agreement with previous results (Maccioni, R.B., Rivas, C., & Vera, J.C. (1988) EMBO J. 7, 1957-1963). The productive interaction of MAP-2 with the latter domain appears to be involved in the assembly of microtubules.

Amino Acid Sequence↗

Teaching and assessing on course for change.

This paper argues that the concept of change is a valuable tool for the development of continuing education which is relevant to the personal needs of nurse practitioners and to clinical practice. The context for this discussion is a teaching and assessing course which holds the concept of change as the central philosophy for curriculum structure. The paper begins by describing the course philosophy, curriculum models and outline structure which typify this course. The second part of the paper describes research used to evaluate the 13 courses which have been held and the main conclusions of this research. It is concluded that this course has proven educational benefits and effects on clinical practice which include the development of critical reflectivity, acceptance of change, increase in self confidence and an increase in self-directed learning.

Curriculum↗

Direct polymerase chain reaction test for detection of Helicobacter pylori in humans and animals.

We designed a polymerase chain reaction (PCR) for amplifying the Helicobacter pylori gene encoding 16S rRNA. Primers for the specific detection of H. pylori were designed for areas of the 16S rRNA gene in which there is the least sequence homology between H. pylori and its closest relatives. The specificity of detection was confirmed by ensuring that the primers did not amplify DNA extracts from the campylobacters H. cinaedi, H. mustelae, and Wolinella succinogenes, which are the closest relatives of H. pylori, as determined by 16S rRNA sequencing. Serial dilution experiments revealed the detection of as little as 0.1 pg of DNA by PCR and 0.01 pg by nested PCR. H. pylori DNA was detected successfully in clinical paraffin-embedded and fresh gastric biopsy specimens from patients positive for the bacterium and also in fecal suspensions seeded with the organism. The DNA from the nonculturable coccoid form of H. pylori was also identified by the primers. Universal primers designed for highly conserved areas on the 16S rRNA gene enabled large amplification products to be produced for direct sequencing analysis. Gastric bacteria resembling H. pylori have been isolated from animals. DNA of these animal gastric bacteria amplified with H. pylori-specific primers yielded PCR products identical to those from human isolates of H. pylori, as confirmed by the use of a 20-base radiolabelled probe complementary to an internal sequence flanked by the H. pylori-specific primers. The results of PCR amplification and partial 16S rRNA gene sequence analysis strongly support the contention that the gastric organisms previously recovered from a pig, a baboon, and rhesus monkeys are H. pylori.

Animals↗