Biomedical subjects
Publications and source records attributed to D L Cook.
A novel method of assessing muscle function in the common marmoset was developed as part of a multidisciplinary long-term study. The method involved home cage presentation of a weight-pulling task. Over a 4-5 month period, 38 of 42 animals were successfully trained to displace weights of up to 920 g (mean 612+/-20 g). Performance, following initial training, was stable and independent of gender or body weight.
Under the Clean Water Action Plan, the US Environmental Protection Agency is requiring states to establish numeric criteria for phosphorus and nitrogen. In preparation for the development of nutrient criteria NCASI undertook a research project to conduct a comparative study of methods for the determination of total phosphorus and total nitrogen in pulp and paper mill matrices. This paper presents results of a single laboratory method evaluation and comparative study of digestion techniques and analytical methods for the determination of total phosphorus (TP) and total nitrogen (TN) in pulp and paper mill secondary treated effluents. Analytical methods included EPA Methods 365.2 and 365.4 for TP. TN and total kjeldahl nitrogen (TKN) methods included EPA Methods 351.2, 351.4, and 353.2. Examinations of sample preservation and storage stability were conducted. Substitution of mercuric sulfate with copper sulfate during block digestion resulted in higher blank levels and method detection limits. TP measurements using EPA Method 365.4 (autoanalyzer) were found to be accurate with a positive bias as determined using matrix spike experiments. Sample digestion by acidic persulfate oxidation or mercuric sulfate block digestion in conjunction with EPA Method 365.4 yielded low blank levels (averages of 0.01 and 0.02 mg/L, respectively), precision of 2.1 and 2.4% relative standard deviations, respectively, and accuracy expressed as an average recovery (%R) of 117% for both. EPA Method 351.2 (autoanalyzer) was more precise than EPA Method 351.4 (ammonia probe). Accuracy (%R) for EPA Method 351.2 ranged from 81 to 95%, depending on the digestion technique applied, and was 55% when EPA Method 351.4 was utilized. Investigation of a method utilizing basic to acidic persulfate oxidation for the simultaneous determination of TN and TP using only two analytical techniques was found to be effective at concentrations above 1 mg/L in pulp mill effluents.
BACKGROUND: We propose that a computerized, internet-based graphical description language for systems biology will be essential for describing, archiving and analyzing complex problems of biological function in health and disease. RESULTS: We outline here a conceptual basis for designing such a language and describe BioD, a prototype language that we have used to explore the utility and feasibility of this approach to functional biology. Using example models, we demonstrate that a rather limited lexicon of icons and arrows suffices to describe complex cell-biological systems as discrete models that can be posted and linked on the internet. CONCLUSIONS: Given available computer and internet technology, BioD may be implemented as an extensible, multidisciplinary language that can be used to archive functional systems knowledge and be extended to support both qualitative and quantitative functional analysis.
Defects in the repair and maintenance of DNA increase risk for cancer. X-ray cross-complementing group 1 protein (XRCC1) is involved with the repair of DNA single-strand breaks. A nucleotide substitution of guanine to adenine leading to a non-conservative amino acid change was identified in the XRCC1 gene at codon 399 (Arg/Gln). This change is associated with higher levels of aflatoxin B1-adducts and glycophorin A somatic mutations. A case-control study was conducted to test the hypothesis that the 399Gln allele is positively associated with risk for adenocarcinoma of the lung. XRCC1 genotypes were assessed at codon 399 in 172 cases of lung adenocarcinoma and 143 cancer-free controls. Two ethnic populations were represented, non-Hispanic White and Hispanic. The distribution of XRCC1 genotypes differed between cases and controls. Among cases, 47.7% were Arg/Arg, 35.5% were Arg/Gln, and 16.9% were Gln/Gln. Among controls, XRCC1 allele frequencies were 45.5% for Arg/Arg, 44.8% for Arg/Gln, and 9.8% for Gln/Gln. Logistic regression analysis was used to assess the association between lung adenocarcinoma and the G/G genotype relative to the A/A or A/G genotypes. In non-Hispanic White participants, the lung cancer risk associated with the G/G genotype increased significantly after adjustment for age (OR=2.81; 95% CI, 1.2-7.9; P=0.03) and increased further after adjustment for smoking (OR=3.25; 95% CI, 1.2-10.7; P=0.03). Among all groups, a significant association was found between the G/G homozygote and lung cancer (OR=2.45; 95% CI, 1.1-5.8; P=0.03) after adjustment for age, ethnicity, and smoking. This study links a functional polymorphism in the critical repair gene XRCC1 to risk for adenocarcinoma of the lung.
The diagnosis of early mycosis fungoides is often regarded as difficult or impossible due to the lack of clear-cut histopathologic criteria. Many authors have published observations of histologic features seen in biopsies of patients with mycosis fungoides and have offered parameters that may be helpful in diagnosis. In the study, undertaken by members of the EORTC Cutaneous Lymphoma Study Group, the proposed histologic features are tested for sensitivity and specificity. This commentary discusses some of the historical issues and the value of the EORTC study pertaining to the diagnosis of early mycosis fungoides.
BACKGROUND: Primary mucinous carcinoma is an uncommon malignant cutaneous tumor which arises most commonly on the eyelid. While rarely causing death, recurrence following primary excision is common and widespread metastasis may occur. OBJECTIVE: We report the first case of bilateral primary mucinous carcinoma of the eyelid. METHODS: A lesion of the left lower eyelid had been resected three times previously with positive conventional margins. Both this lesion and a second primary lesion of the contralateral lower lid were removed with Mohs microscopically controlled excision without recurrence for more than 2 years. CONCLUSION: Multiple lesions of mucinous carcinoma of the eyelid do not necessarily connote metastasis. Mohs microscopically controlled excision may be a suitable form of therapy for primary mucinous carcinoma of the eyelid.
Disseminated Acanthamoeba infections are almost invariably fatal, with no universally accepted standard for treatment. Reports of acanthamoebiasis in non-human-immunodeficiency-virus infected hosts are rare. We successfully treated a lung transplant patient who had disseminated acanthamoebiasis using a combination of pentamidine, 5-fluorocytosine, itraconazole, and topical chlorhexidine gluconate/ketoconazole cream.
During dissection of a cadaver at the Ohio College of Podiatric Medicine, the authors encountered the os subfibulare. The os subfibulare was encased within the peroneus longus and peroneus brevis tendons and initially appeared as though it may have articulated with the left lateral malleolus distally and posteriorly. The ossicle was not associated with any capsular or ligamentous structures. These findings suggest that the os subfibulare is a true sesamoid bone. A review of the literature is presented and the clinical significance of these findings is discussed.
There is increasing recognition that stochastic processes regulate highly predictable patterns of gene expression in developing organisms, but the implications of stochastic gene expression for understanding haploinsufficiency remain largely unexplored. We have used simulations of stochastic gene expression to illustrate that gene copy number and expression deactivation rates are important variables in achieving predictable outcomes. In gene expression systems with non-zero expression deactivation rates, diploid systems had a higher probability of uninterrupted gene expression than haploid systems and were more successful at maintaining gene product above a very low threshold. Systems with relatively rapid expression deactivation rates (unstable gene expression) had more predictable responses to a gradient of inducer than systems with slow or zero expression deactivation rates (stable gene expression), and diploid systems were more predictable than haploid, with or without dosage compensation. We suggest that null mutations of a single allele in a diploid organism could decrease the probability of gene expression and present the hypothesis that some haploinsufficiency syndromes might result from an increased susceptibility to stochastic delays of gene initiation or interruptions of gene expression.
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Hope is the sum of goal thoughts as tapped by pathways and agency. Pathways reflect the perceived capability to produce goal routes; agency reflects the perception that one can initiate action along these pathways. Using trait and state hope scales, studies explored hope in college student athletes. In Study 1, male and female athletes were higher in trait hope than nonathletes; moreover, hope significantly predicted semester grade averages beyond cumulative grade point average and overall self-worth. In Study 2, with female cross-country athletes, trait hope predicted athletic outcomes; further, weekly state hope tended to predict athletic outcomes beyond dispositional hope, training, and self-esteem, confidence, and mood. In Study 3, with female track athletes, dispositional hope significantly predicted athletic outcomes beyond variance related to athletic abilities and affectivity; moreover, athletes had higher hope than nonathletes.
Increasing numbers of minorities are seeking mental health assistance. Inclusion of cultural considerations is important for increasing sensitivity to those whose life experiences differ. For African Americans, therapy is better facilitated if one operates from a cultural specific frame of reference. African American women attending a women's support group were surveyed. Questionnaires querying dimensions on family relationships, self-esteem and dependency were utilized. Results indicated a relationship between social support, self-esteem and codependency in African American females. Social support and self-esteem were inversely associated with codependency. This study provides insight for mental health professionals in counseling African American females.
Treatment for diabetes can range from balancing a meal plan to maintaining a complex insulin regime. Without allocating large amounts of time and resources, home care providers can take steps to improve service delivery to patients with diabetes.
This review describes the role of sulfonylureas and ATP-sensitive K channels (KATP) in controlling glucose-induced membrane electrical activity in pancreatic beta-cells. The glucose-dependent pathway, the most important both physiologically and pathophysiologically, is contrasted with other pathways for non-nutrient beta-cell modulators. KATP channels, the links between beta-cell metabolism and membrane electrical activity, are regulated in complex ways by nucleotide phosphates and a number of clinically important pharmacological agents. Recent cloning of the islet sulfonylurea receptor and KATP channel should lead to answers to important questions raised by 25 years of beta-cell electrophysiology.
Medullary carcinoma (MC) of the breast has been regarded as a subtype of breast carcinoma with a relatively favorable prognosis despite its high nuclear grade and high mitotic index. High nuclear grade and high mitotic index have been correlated with DNA aneuploidy and high S-phase fraction (SPF) by flow cytometry. Generally in breast cancer, these histologic and DNA content features predict a less favorable prognosis. To address this paradox, all cases of MC of the breast (20 of 1,365 carcinomas [1.5%]) diagnosed between 1968 and 1982 were compared to age- and stage-matched cases of infiltrating ductal carcinoma (IDC) diagnosed during the same time period. All of the MC and 80% of the IDC had one or more DNA aneuploid stem lines. Average total SPF was 8.1% for MC and 4.8% for IDC. DNA analysis was performed from paraffin blocks (average CV: 4.5% DNA diploid; 4.1% DNA aneuploid), and subjected to computer modeled analysis. Statistically significant differences between presence or absence of DNA aneuploidy (P = .035) and total SPF (P = .029) were demonstrated between the two groups. Thirteen of 20 patients (65%) with MC (average followup 130 months) were alive at the end of the study period compared to 12 of 20 patients (60%) with IDC (average follow-up 160 months). The difference in crude survival was not statistically significant (P = .867). However, there was a tendency toward early death in MC and late death in IDC. Within the TNM stage-matched patients, no significant difference was demonstrated for tumor size or nodal status when these variables were examined separately. In conclusion, statistically significant differences in DNA content and proliferative fraction exist between medullary carcinoma of the breast and ductal carcinoma. The biologic and clinical differences demonstrated in this analysis warrant careful consideration before including cases of medullary carcinoma in studies evaluating newer prognostic variables in breast cancer.
To determine the potential for differential release of islet amyloid polypeptide and insulin, we performed studies in rat islet monolayer cultures under conditions known to impair regulated beta-cell secretion. In inhibiting concentrations of epinephrine or the absence of calcium, islet amyloid polypeptide was secreted through a constitutive pathway while insulin was not. These findings suggest a mechanism for persistent islet amyloid polypeptide secretion and amyloid accumulation when regulated insulin release is impaired as in Type 2 (non-insulin-dependent) diabetes mellitus and insulinomas.
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