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PubMed1996

Comprehensive and accurate mutation scanning of the CFTR gene by two-dimensional DNA electrophoresis.

The large number of possible disease-causing mutations in the 27 exons of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has severely limited direct diagnosis of cystic fibrosis (CF) patients and carriers by mutation detection. Here we show that in principle testing for mutations in the CFTR gene can be both substantially facilitated and made virtually complete, by two-dimensional DNA electrophoretic separation of polymerase chain reaction (PCR) amplified exons on the basis of size and basepair sequence in denaturing gradient gels. Under a single optimized set of conditions we were able to obtain a pattern of spots representing all 27 exons of the CFTR gene and to readily detect 17 out of 17 identified sequence variations in 9 different exons in DNA from 11 CF patients and carriers. Our results demonstrate the potential of 2-dimensional DNA electrophoresis for comprehensive mutation analysis of the CFTR gene. The approach serves as a model for comprehensive diagnosis of the many other large disease genes for which a variety of mutations have also which been reported.

Cystic Fibrosis↗

PubMed1989

Integration of pain management into comprehensive cancer care.

Pain management is an integral component of comprehensive cancer care. Designing an effective pain control strategy for the individual patient requires knowledge of the ways in which a patient's cancer, cancer therapy, and pain therapy can interact. Two important aspects of cancer that affect the way in which pain is managed are the cancer's treatability and components of its pathophysiology that themselves do not cause pain (the cancer's "nonpain" pathophysiology). Cancer treatability modifies the need for pain management and the appropriateness of invasive pain procedures. Cancer nonpain pathophysiology can interfere with the oral administration of medications, narrow the patient's therapeutic window for analgesic drugs, limit the effectiveness of psychologic pain therapies, and complicate or preclude invasive pain-relieving procedures. In addition, cancer therapy can interfere with or enhance pain therapy and vice versa. Cancer therapy can interfere with pain therapy by causing pain or by producing other adverse effects. Cancer therapy can enhance pain therapy by reducing the extent of cancer, by acting as a coanalgesic, and by providing intravenous access for parenteral drug administration to patients who require it. Pain therapy can interfere with cancer therapy by increasing or complicating the adverse effects of cancer therapy. Pain therapy can enhance cancer therapy by improving patient performance, and certain palliative surgical procedures may have the ancillary effect of improving organ function. Five case descriptions are presented as illustrations of effective integration of pain management into comprehensive cancer care.

Adenocarcinoma↗

PubMed1991

Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging.

Forty-nine women with apparent Stage I and II ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as the first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.

Chromium↗

PubMed1995

Public education projects in skin cancer. The evolution of skin cancer prevention education for children at a comprehensive cancer center.

BACKGROUND: Skin cancer affects more Americans than any other type of cancer. Children are prime targets for prevention education, because sun overexposure in early childhood may affect the development of skin cancer later in life. Preventive behaviors adopted early in life may be less resistant to change than those acquired in adulthood. Thus, there is a need to educate children at an early age about sun overexposure. METHODS: This article describes the evolution of skin cancer prevention research at the Arizona Cancer Center, a National Cancer Institute--designated comprehensive cancer center. Research focusing on children is high-lighted. RESULTS: From its roots in the Arizona Sun Awareness Project, an informal public skin cancer education program, skin cancer prevention research at the Arizona Cancer Center has produced two developmentally appropriate, age-based curricula aimed at teaching children about the benefits and dangers of the sun. The elementary school curriculum, Sunny Days, Healthy Ways, has undergone two tests of feasibility and is the intervention used in a large, randomized, experimental trial. The preschool curriculum, Be Sun Safe, has been tested in a randomized trial and was found to have a positive effect on preschoolers' knowledge and comprehension of sun safety. CONCLUSIONS: Educating children about skin cancer may be an important way of decreasing the incidence of skin cancer. Although informal skin cancer prevention education can be helpful, educational programs preferably should be research based and evaluated for effectiveness before public distribution. The Arizona Cancer Center experience can serve as a model for other programs.

Adolescent↗

PubMed2000

Observations on the reproducibility and matching efficiency of two-dimensional electrophoresis gels: consequences for comprehensive data analysis.

Protein expression profiling by proteomics has the potential to be an ideal tool for the description of changes in complex biological systems or in the characterization of a disease. This study analyzes in more quantitative terms how methodological drawbacks of the current technology can hamper the comprehensive analysis of large sets of spot patterns by statistical means. Irreproducibilities in spot intensities due to silver staining and geometric distortions of the spot patterns inherent to the electrophoresis procedure push even the semiautomatic alignment and matching to their limits. This leads to reduced matching efficiencies for identical spots if no additional exhaustive manual matching is performed for every single spot in all gels. As a consequence, only a limited number of spots can be matched in all gels of a large set. The statistical pattern analysis of such data sets will thus not allow the comprehensive description of relevant pattern changes.

Electrophoresis, Gel, Two-Dimensional↗

PubMed1990

Delineation of single-word semantic comprehension deficits in aphasia, with anatomical correlation.

In 3 of 18 aphasic patients pure deficits in semantic comprehension at the single-word level were defined through a series of tasks that excluded possible confounding deficits in auditory perception, visual perception, or speech production. In these pure cases, deficits were found at the superordinate, equivalence, and subordinate levels of single-word semantic processing. Pure semantic deficits were found to be correlated with damage to the left posterior temporal and inferior parietal region; patients whose damage spared this area did not evince such deficits, and the converse was also true. This study confirms the existence of separable deficits in semantic comprehension and points conclusively to the left posterior temporal and inferior parietal region as being critical for semantic processing. This anatomical localization is in keeping with anatomical studies from nonhuman primates, suggesting that these regions may be concerned with multimodal processing and integration of language.

Aphasia↗

PubMed2003

Comprehensive strategy for chiral separations using sulfated cyclodextrins in capillary electrophoresis.

This review focuses on the emerging role of sulfated cyclodextrins in the capillary electrophoretic (CE) separation of chiral analytes. Since being introduced as enantioselective agents for CE in 1995, these anionic additives have continued to demonstrate remarkable application universality. The broad spectrum of chiral compounds successfully separated using this approach includes acidic, basic, neutral, and zwitterionic species. This impressive array of analyte structures is derived from a growing diversity of compound classes including pharmaceuticals, plant extracts, biomarkers, herbicides, alkaloids, fungicides, and metal ions. Moreover, literature reports highlight the minimal optimization required to achieve a successful separation. Based on these findings, sulfated cyclodextrins appear to be well suited for the development of a more universal, comprehensive separation strategy for chiral compounds. This review explores this proposition by beginning with the structure and migration properties of sulfated cyclodextrins, using applications to highlight the separating power of this technique and ending with a pragmatic, comprehensive separation strategy.

Animals↗

PubMed2000

Need for comprehensive women's health continuing medical education among primary care physicians.

BACKGROUND: The Council on Graduate Medical Education's (COGME) Fifth Report on Women and Medicine states that "changes in undergraduate and graduate medical education, in addition to continuing medical education, are needed to address adequately the comprehensive health needs of women." Primary care physicians (PCPs) who completed residency training prior to the establishment of new guidelines for women's health education are dependent on continuing medical education (CME) to update their knowledge and skills. METHODS: Primary care physicians attending a university-based CME program in family medicine were surveyed (n = 300) about their need for CME in women's health topics. Responses were analyzed using chi-square analysis and Pearson correlations. Topics of interest were compared with women's health competencies published in 1997 by the American Board of Internal Medicine (ABIM) and in 1997 by the American Academy of Family Physicians (AAFP). RESULTS: Of 30 women's health topics listed, 22 were of interest to 50% or more of respondents and 11 were of very high interest (p < .05). Respondents most interested in women's health CME were most likely to believe CME would reduce the number of referrals currently required to evaluate women's breast problems. Topics of interest also align well with ABIM and AAFP competencies in women's health. CME in comprehensive women's health care is therefore of high interest to our respondents and topics of greatest interest are identified. IMPLICATIONS: Areas of interest correlate well with new requirements by ABIM and AAFP and should be targeted by CME programs.

Education, Medical, Continuing↗

PubMed2002

Physical exercise and immune system function in cancer survivors: a comprehensive review and future directions.

BACKGROUND: There are a limited number of interventions for cancer survivors following completion of primary therapy that might reduce the risk of cancer recurrence and/or secondary malignancies and increase survival times. It has been proposed that physical exercise may be beneficial by enhancing the anticancer immune system response. The purpose of the current article is to: 1) briefly describe the immune system response to tumors, 2) discuss the impact of anticancer therapy on immune system function in cancer survivors, 3) provide a systematic and comprehensive review of the extant literature examining physical exercise and immune system function in cancer survivors, and 4) offer a critical analysis of this literature and outline directions for future research. METHODS: A comprehensive literature search up to March 2001 identified empirical articles that examined the effects of physical exercise training on immune system function in cancer survivors from CD-ROM database searches and manual searches. RESULTS: To the authors' knowledge, six empirical studies published between 1994 and 2000 have examined physical exercise and immune system function in cancer survivors. Overall, four out of six studies reported statistically significant improvements in a number of cancer-related immune system components as a result of exercise. However, there are several limitations that must be considered when interpreting the findings of these studies. These limitations involve the samples, designs, physical exercise interventions, physical fitness assessments, and immunologic assessments. CONCLUSIONS: Additional research is needed to determine if physical exercise in cancer survivors may reduce the risk of cancer recurrence and secondary malignancies and increase survival times.

Adult↗

PubMed1991

Primary prevention of cancer. The case for comprehensive school health education.

Comprehensive school health education plays an important role in the primary prevention of cancer because so many of the health habits relating to cancer and other diseases have their onset early in life. A comprehensive health education program should begin early in life. Such education must be multifactorial from kindergarten through high school, should involve annual health screening, must be assessed annually, and is most effective when coordinated by a full-time health education teacher. Those concerned about the many problems of health behavior in our society should insist that such programs become mandatory in every state in this nation.

Adolescent↗

PubMed2006

A chip-based miniaturized format for protein-expression profiling: the exploitation of comprehensively produced antibodies.

Numerous antibodies have been developed and validated in recent years, and show promise for use in novel functional protein assays. Such assays would be an alternative to pre-existing comprehensive assays, such as DNA microarrays. Antibody microarrays are thought to represent those functional protein assays. While a variety of attempts have been made to apply DNA microarray technology to antibody microarrays, a fully optimized protocol has not been established. We have been conducting a project to comprehensively produce antibodies against mouse KIAA ("KI" stands for "Kazusa DNA Research Institute" and "AA" are reference characters) proteins. Using our library of antibodies, we established a novel antibody microarray format that utilizes surface plasmon resonance (SPR) technology. A label-free real-time measurement of protein expression in crude cell lysates was achieved by direct readout of the bindings using SPR. Further refinement of the antibody microarray format enabled us to detect a smaller quantity of target proteins in the lysate without the bulk effect. In this review, we first summarize available antibody array formats and then describe the above-mentioned format utilizing updated SPR technology.

Animals↗

PubMed1992

Polymerase chain reaction-based comprehensive procedure for the analysis of the mutation spectrum at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster cells.

We have established a comprehensive procedure based on the polymerase chain reaction (PCR) to analyze the molecular spectrum of mutations at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in Chinese hamster cells. The procedure includes direct sequencing of PCR-amplified hprt cDNA for locating point mutations in the expressed coding sequences, multiplex PCR amplification of the hprt exons for screening large deletions, and direct sequencing of PCR-amplified hprt exons and their flanking regions for detecting intronic mutations resulting in mRNA splicing errors. Using this procedure, we have identified different types of mutations among a representative collection of spontaneous and induced HPRT-deficient Chinese hamster cell mutants. This procedure is simple, rapid, accurate, and practical for a comprehensive study of the mutation spectrum in a large number of HPRT-deficient Chinese hamster cell mutants.

Animals↗

PubMed2002

Comprehensive karyotyping of the HT-29 colon adenocarcinoma cell line.

The tumor cell line HT-29 was derived from a primary adenocarcinoma of the rectosigmoid colon. HT-29 is hypertriploid (3n+) and has accumulated numerous chromosomal structural aberrations. To identify material involved in chromosome rearrangements, we performed a comprehensive cytogenetic analysis using G-banding, spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH). The combination of molecular cytogenetic techniques enabled us to define the first comprehensive karyotype for HT-29. Seventeen marker chromosomes were found in 75-100% of metaphase cells, generally in a single copy per cell. We confirmed the composition of eight previously described markers, refined the classification of seven others, and identified two novel marker chromosomes. Notable aberrations included a reciprocal translocation between chromosomes 6 and 14 and an unusual, large derivative chromosome 8 composed entirely of 8q material. The telomere status, evaluated by FISH, revealed telomeric signals at the termini of all chromosomes. No interstitial telomeric sequences were observed in any cell. Although numerous chromosomal aberrations are present in HT-29, the cell line appears to have retained a high level of genomic stability during passage in culture since undergoing transformation. The excellent resolving power of SKY, coupled with additional information obtained from molecular cytogenetic analyses, will improve our ability to identify genetic lesions characteristic of cancer.

Adult↗

PubMed2002

Modality independence of word comprehension.

Functional magnetic resonance imaging (fMRI) was used to examine the functional anatomy of word comprehension in the auditory and visual modalities of presentation. We asked our subjects to determine if word pairs were semantically associated (e.g., table, chair) and compared this to a reference task where they were asked to judge whether word pairs rhymed (e.g., bank, tank). This comparison showed task-specific and modality-independent activation for semantic processing in the heteromodal cortices of the left inferior frontal gyrus (BA 46, 47) and left middle temporal gyrus (BA 21). There were also modality-specific activations in the fusiform gyrus (BA 37) for written words and in the superior temporal gyrus (BA 22) for spoken words. Our findings are consistent with the hypothesis that word form recognition (lexical encoding) occurs in unimodal cortices and that heteromodal brain regions in the anterior as well as posterior components of the language network subserve word comprehension (semantic decoding).

Adult↗

PubMed2004

Comprehensive decision analytical modelling in economic evaluation: a Bayesian approach.

Decision analytical models are widely used in economic evaluation of health care interventions with the objective of generating valuable information to assist health policy decision-makers to allocate scarce health care resources efficiently. The whole decision modelling process can be summarised in four stages: (i) a systematic review of the relevant data (including meta-analyses), (ii) estimation of all inputs into the model (including effectiveness, transition probabilities and costs), (iii) sensitivity analysis for data and model specifications, and (iv) evaluation of the model. The aim of this paper is to demonstrate how the individual components of decision modelling, outlined above, may be addressed simultaneously in one coherent Bayesian model (sometimes known as a comprehensive decision analytical model) and evaluated using Markov Chain Monte Carlo simulation implemented in the specialist software WinBUGS. To illustrate the method described, it is applied to two illustrative examples: (1) The prophylactic use of neurominidase inhibitors for the prevention of influenza. (2) The use of taxanes for the second-line treatment of advanced breast cancer. The advantages of integrating the four stages outlined into one comprehensive decision analytical model, compared to the conventional 'two-stage' approach, are discussed.

Adolescent↗

PubMed2002

Novel mutations and SNPs identified in CCR2 using a new comprehensive denaturing gradient gel electrophoresis assay.

A single nucleotide polymorphism (SNP) at codon 64 in the CC chemokine receptor 2 gene (CCR2 V64I) has been associated with a dominant effect of delaying disease progression from human immunodeficiency virus-1 (HIV-1) infection to acquired immunodeficiency syndrome (AIDS). The objective of our study was to design a comprehensive mutation detection assay for the entire coding region of the CCR2A and CCR2B gene transcripts, including all relevant splice site junctions and to identify novel mutations and SNPs within our predominantly African-based population, which could influence an individual's susceptibility to HIV-1 infection and/or progression to AIDS. The mutation detection assay, based on denaturing gradient gel electrophoresis (DGGE), allowed for the complete analysis of five individuals per denaturing gel. Our study cohort consisted of 102 HIV seropositive patients and 144 HIV seronegative controls from the diverse South African population. Application of the CCR2-DGGE assay resulted in the detection of two previously reported CCR2 polymorphisms, namely CCR2 V64I and CCR2 N260N, and 11 novel mutations, including seven SNPs occurring at high allelic frequencies within specific population groups of South Africa. The large number of novel mutations/SNPs identified, using the CCR2-DGGE assay, indicates the importance for comprehensive analysis of all candidate genes in host susceptibility to HIV-1 infection, specifically in the under-studied African-based populations.

Amino Acid Substitution↗

PubMed2006

Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism characterized by accumulation of glycine in body fluids and various neurological symptoms. NKH is caused by deficiency of the glycine cleavage multi-enzyme system with three specific components encoded by GLDC, AMT, and GCSH. We undertook the first comprehensive screening for GLDC, AMT, and GCSH mutations in 69 families (56, six, and seven families with neonatal, infantile, and late-onset type NKH, respectively). GLDC or AMT mutations were identified in 75% of neonatal and 83% of infantile families, but not in late-onset type NKH. No GCSH mutation was identified in this study. GLDC mutations were identified in 36 families, and AMT mutations were detected in 11 families. In 16 of the 36 families with GLDC mutations, mutations were identified in only one allele despite sequencing of the entire coding regions. The GLDC gene consists of 25 exons. Seven of the 32 GLDC missense mutations were clustered in exon 19, which encodes the cofactor-binding site Lys754. A large deletion involving exon 1 of the GLDC gene was found in Caucasian, Oriental, and black families. Multiple origins of the exon 1 deletion were suggested by haplotype analysis with four GLDC polymorphisms. This study provides a comprehensive picture of the genetic background of NKH as it is known to date.

Adolescent↗

PubMed1994

Binge eating disorder affects outcome of comprehensive very-low-calorie diet treatment.

To determine the effects of binge eating disorder (BED) on weight loss and maintenance in women undergoing treatment for obesity, we studied the weight changes of 38 women (body mass index > 30 kg/m2), 21 of whom met proposed criteria for BED and 17 of whom reported few problems with binge eating, during and after a 26-week comprehensive very-low-calorie diet (VLCD) treatment program. All 17 subjects without and 16/21 subjects with BED returned for four follow-up visits over 12 months (p = 0.05). While a similar proportion of subjects with and without BED reported absolute adherence to both the modified fast and refeeding, those with BED showed a significantly different distribution in energy intake from those without BED, with fewer small and more large lapses among those who deviated from the diet (p < 0.05). There was no significant difference in mean weight loss over the 26 weeks of treatment, but subjects with BED showed significantly diminished weight loss during the middle third of treatment (p < 0.05). Black subjects, regardless of the presence of BED, lost significantly less weight during treatment than white subjects (p < 0.005). Although there was no significant difference in mean weight loss at any of the four follow-up visits between subjects with and without BED, 25% of subjects with BED had regained > 50% of their lost weight by three-month follow-up, vs. no subjects without the disorder (p < 0.05). One year after completing treatment, approximately half of BED (+) and BED (-) subjects had a good outcome, maintaining a weight loss > or = 10% of initial body weight. However, 35% of subjects with BED, and none of the subjects without BED, had a poor outcome (p < 0.05). We conclude that many individuals with BED will respond well to a medically supervised comprehensive VLCD program, attaining medically significant weight loss. However, this subgroup appears to be at risk for early major regain of lost weight and for poor outcome one year following weight-loss treatment.

Adolescent↗