Biomedical subjects

Dan Moore

Publications and source records attributed to Dan Moore.

At least 19 recordsLinked to original sources

PubMed2006

A father of four consecutive trisomic pregnancies with elevated frequencies of associated aneuploid sperm.

A couple with normal somatic karyotypes had four consecutive trisomic pregnancies, each involving a different chromosome, of which two children were liveborn with confirmed paternal-origin trisomies. The apparently healthy father produced abnormally high frequencies of disomic sperm for each of the four chromosomes involved in the trisomic pregnancies (P< 0.003, by sperm fluorescence in situ hybridization (FISH)). His elevated sperm aneuploidies persisted over a 2-year period and affected all chromosomes evaluated, suggesting that he had a genome-wide defect in meiotic disjunction. He also had the highest frequencies of aneuploid sperm reported for any healthy man to date. His frequencies of aneuploid sperm were comparable to the peak frequencies of the transient responses reported in some cancer patients after receiving aneugenic chemotherapies. These findings indicate that apparently healthy men can produce abnormally high frequencies of sperm aneuploidies that suggest that this condition may contribute to recurrent trisomic pregnancies.

Adult↗

PubMed2006

Evaluation of a visit preparation intervention implemented in two rural, underserved counties of Northern California.

OBJECTIVE: Evaluate satisfaction with visit preparation at three rural resource center sites. METHODS: The resource centers sent eight employees and two volunteers for training at UCSF in Consultation Planning (CP). CP is a service to help patients make a list of questions before seeing their doctors. Researchers used multivariate ordered logistic regression analysis to investigate the variation in satisfaction among 99 CP Clients served by the resource centers in 2003. RESULTS: Sixty-seven CP Clients who completed surveys were highly satisfied (mean=8.67, standard deviation (S.D.)=1.85, range=5-10). Variation in satisfaction was associated only with whether or not the CP Provider was a breast cancer survivor serving a breast patient (p=0.005). Satisfaction was not associated with CP Client demographics; type of upcoming medical visit; or CP Provider age, remuneration status, nursing background, and volume of CP Clients. CONCLUSION: Community-based resource centers have implemented CP to the satisfaction of their clients. Further research should expand the delivery of CP to more underserved members of the community and evaluate its acceptability and impact. There may be a therapeutic alliance formed when survivors provide CP to newly diagnosed patients. PRACTICE IMPLICATIONS: CP should be considered by patient support programs wishing to expand their client services to include visit preparation.

Adult↗

PubMed2006

Independent motile microplast formation correlates with glioma cell invasiveness.

Diffuse brain invasion contributes to the poor prognosis for patients with gliomas. Analyzing glioma cell migration in vitro, we have demonstrated the spontaneous shedding of anucleate cell fragments that separate from glioma cell bodies and maintain viability from hours to days. Unlike previously described cell fragments that are released from cells as diffusible vectors, glioma cell fragments are independently motile. We used computerized time-lapse microscopy to characterize the formation of these independent motile microplasts (IMMPs) in human cell cultures derived from the most highly invasive glial tumor, glioblastoma. IMMPs were larger than previously described cell fragments, ranging in size from approximately 2% to nearly half of the area of their parent cells. Complex cell-like behaviors-including establishment of polarity, extension of lamellipodia and filopodia, and change in direction of movement-remained intact in IMMPs. The average direction and velocity of the IMMPs were indistinguishable from those of their parent cells. IMMPs formed at a significantly higher rate in glioma cell lines rendered more invasive by overexpression of invasion-related genes than in vector-transfected controls. The correlation with cell invasiveness indicates that IMMP formation may be related to the cell-invasive phenotype. Further investigation will determine whether IMMPs represent a novel addition to the growing list of viable cell fragments with biological relevance.

Astrocytoma↗

PubMed2006

Is there a useful cesarean birth measure? Assessment of the nulliparous term singleton vertex cesarean birth rate as a tool for obstetric quality improvement.

OBJECTIVE: This study was undertaken to assess the utility of the nulliparous term singleton vertex cesarean birth (NTSV CB) measure as a quality improvement tool for use at the hospital level. STUDY DESIGN: We prospectively collected data on all NTSV births in Sutter Health's 20 birthing units over a 3-year period, 2001 through 2003, totaling 41,416 births. Hospital rates of NTSV CB, obstetric practices, and infant outcomes were calculated and compared by using weighted logistic analyses. In addition, we examined the effect of maternal age on the NTSV CB measure by using direct standardization with US norms for nulliparous women. RESULTS: There was large variation noted in the NTSV CB rate among the 20 hospitals, with unadjusted rates ranging from 10.5% to 30.2%. Strong correlations were found between CB rates and labor induction rates (r = 0.57, P < .0001) and with early labor admission rates (r = 0.62, P < .0001). The strongest correlation was found between NTSV CB rates and a combined measure of induction and early labor admission (r = 0.73, P < .0001). Rates of term 5-minute Apgar score below 7 were not correlated with the NTSV CB rate. Hospital nulliparous maternal age distribution varied markedly and direct standardization led to significant changes in the NTSV CB rate. CONCLUSION: NTSV CB rate is strongly influenced by elective obstetric practices. The addition of an easily performed maternal age adjustment makes it the most promising CB quality measure for use at the hospital level.

Birth Rate↗

PubMed2006

Altered promoter usage characterizes monoallelic transcription arising with ERBB2 amplification in human breast cancers.

Analysis of a collection of human breast cancers (n = 150), enriched in ERBB2-positive cases (n = 57) and involving tumor genotyping relative to population-matched blood genotyping (n = 749) for a common ERBB2 single nucleotide polymorphism Ala(G)1170Pro(C), revealed that ERBB2 amplification in breast cancer is invariably monoallelic. Analysis of paired breast cancer and blood samples from informative (G1170C heterozygotic) ERBB2-positive (n = 12) and ERBB2-negative (n = 17) cases not only confirmed monoallelic amplification and ERBB2 transcriptional overexpression but also revealed that most low ERBB2 expressing breast cancers (12/17) exhibit unbalanced allelic transcription, showing 3-fold to nearly 5,000-fold preferential expression from one of two inherited alleles. To explore cis-acting transcriptional mechanisms potentially selected during ERBB2 amplification, levels of four different ERBB2 transcript variants (5.2, 4.7, 2.1, and 1.4 kb) were correlated with total (4.6 kb) ERBB2 mRNA levels in ERBB2-positive (n = 14) versus ERBB2-negative (n = 43) primary breast cancers. Relative expression of only the 2.1 kb extracellular domain-encoding splice variant and a 4.7 kb mRNA variant that uses an alternative start site were significantly increased in association with ERBB2-positivity, implicating altered promoter usage and selective transcript regulation within the ERBB2 amplicon. Altogether, these findings provide new mechanistic insights into the development of ERBB2-positive breast cancer and strong rationale for delineating candidate cis-acting regulatory elements that may link allele-specific ERBB2 transcription in premalignant breast epithelia with subsequent development of breast cancers bearing monoallelic ERBB2 amplicons.

Alleles↗

PubMed2006

Valerian for sleep: a systematic review and meta-analysis.

Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of the roots of valerian (Valeriana officinalis) are widely used for inducing sleep and improving sleep quality. A systematic review of randomized, placebo-controlled trials of valerian for improving sleep quality is presented. An extensive literature search identified 16 eligible studies examining a total of 1093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% confidence interval, 1.2-2.9), but there was evidence of publication bias in this summary measure. The available evidence suggests that valerian might improve sleep quality without producing side effects. Future studies should assess a range of doses of standardized preparations of valerian and include standard measures of sleep quality and safety.

Humans↗

PubMed2005

Array comparative genomic hybridization identifies genetic subgroups in grade 4 human astrocytoma.

Alterations of DNA copy number are believed to be important indicators of tumor progression in human astrocytoma. We used an array of bacterial artificial chromosomes to map relative DNA copy number in 50 primary glioblastoma multiforme tumors at approximately 1.4-Mb resolution. We identified 33 candidate sites for amplification and homozygous deletion in these tumors. We identified three major genetic subgroups within these glioblastoma multiforme tumors: tumors with chromosome 7 gain and chromosome 10 loss, tumors with only chromosome 10 loss in the absence of chromosome 7 gain, and tumors without copy number change in chromosomes 7 or 10. The significance of these genetic groups to therapeutics needs further study.

Brain Neoplasms↗

PubMed2005

Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients.

PURPOSE: To examine the relationship of epidermal growth factor receptor (EGFR) expression to ErbB-2 signaling activity in breast cancer and the impact that this interaction has on the prognosis of patients with early-stage breast cancer. PATIENTS AND METHODS: Paraffin tumor sections were collected retrospectively from 807 breast cancer patients diagnosed between 1976 and 1983. Immunohistochemical assays for ErbB-2, phosphorylated (activated) ErbB-2, and EGFR were performed, and the results were correlated with clinicopathologic variables and outcome. RESULTS: EGFR expression was detectable in 15% of 807 invasive breast cancers, including 35% of the 306 ErbB-2-positive patients. Conversely, the majority (87%) of EGFR-positive tumors co-overexpressed ErbB-2. Ninety-seven percent of tumors with phosphorylated ErbB-2 co-overexpressed EGFR. Patients whose cancers demonstrated ErbB-2 phosphorylation or co-overexpression of ErbB-2 and EGFR had the shortest survival. In contrast, patients whose tumors were negative for all three markers and those tumors that expressed only EGFR or only nonphosphorylated ErbB-2 had a relatively favorable outcome. CONCLUSION: These data provide the first clinical evidence that EGFR expression is linked to activation of ErbB-2 in human breast cancers. We have further shown that the adverse prognostic value of ErbB-2 overexpression is observed only when ErbB-2 is in the phosphorylated (activated) state or coexpressed with EGFR. These data suggest that ligand-dependent mechanisms of ErbB-2 activation are important in human breast cancer. These results also suggest that agents targeting EGFR may be useful in the treatment of tumors with activated ErbB-2.

Biomarkers, Tumor↗

PubMed2005

Time-lapse analysis of potential cellular responsiveness to Johrei, a Japanese healing technique.

BACKGROUND: Johrei is an alternative healing practice which involves the channeling of a purported universal healing energy to influence the health of another person. Despite little evidence to support the efficacy of such practices the use of such treatments is on the rise. METHODS: We assessed cultured human cancer cells for potential responsiveness to Johrei treatment from a short distance. Johrei treatment was delivered by practitioners who participated in teams of two, alternating every half hour for a total of four hours of treatment. The practitioners followed a defined set of mental procedures to minimize variability in mental states between experiments. An environmental chamber maintained optimal growth conditions for cells throughout the experiments. Computerized time-lapse microscopy allowed documentation of cancer cell proliferation and cell death before, during and after Johrei treatments. RESULTS: Comparing eight control experiments with eight Johrei intervention experiments, we found no evidence of a reproducible cellular response to Johrei treatment. CONCLUSION: Cell death and proliferation rates of cultured human cancer cells do not appear responsive to Johrei treatment from a short distance.

Brain Neoplasms↗

PubMed2005

Array-based comparative genomic hybridization from formalin-fixed, paraffin-embedded breast tumors.

Identification of prognostic and predictive genomic markers requires long-term clinical follow-up of patients. Extraction of high-quality DNA from archived formalin-fixed, paraffin-embedded material is essential for such studies. Of particular importance is a robust reproducible method of whole genome amplification for small tissue samples. This is especially true for high-resolution analytical approaches because different genomic regions and sequences may amplify differentially. We have tested a number of protocols for DNA amplification for array-based comparative genomic hybridization (CGH), in which relative copy number of the entire genome is measured at 1 to 2 mb resolution. Both random-primed amplification and degenerate oligonucleotide-primed amplification approaches were tested using varying amounts of fresh and paraffin-extracted normal and breast tumor input DNAs. We found that random-primed amplification was clearly superior to degenerate oligonucleotide-primed amplification for array-based CGH. The best quality and reproducibility strongly depended on accurate determination of the amount of input DNA using a quantitative polymerase chain reaction-based method. Reproducible and high-quality results were attained using 50 ng of input DNA, and some samples yielded quality results with as little as 5 ng input DNA. We conclude that random-primed amplification of DNA isolated from paraffin sections is a robust and reproducible approach for array-based CGH analysis of archival tumor samples.

Breast Neoplasms↗

PubMed2004

Nicotine enhances trace cued fear conditioning but not delay cued fear conditioning in C57BL/6 mice.

Nicotine facilitates hippocampus-dependent contextual but not hippocampus-independent cued delay fear conditioning. To test if the effects of nicotine are specific to contextual fear conditioning or would extend to another hippocampus-dependent version of fear conditioning, we compared the effects of nicotine on cued delay and cued trace fear conditioning in male and female C57BL/6 mice. Unlike cued delay fear conditioning, cued trace fear conditioning is hippocampus dependent. Thus, if nicotine enhances hippocampus-dependent fear conditioning, nicotine should enhance trace fear conditioning. For both trace and delay conditioning, five 30 s, 85 dB white noise conditioned stimuli (CS) were paired with five 2 s, 0.5 mA footshock unconditioned stimuli (US). In the trace paradigm, a 30-s period was inserted between CS offset and US onset. The CS and US co-terminated in the delay paradigm. Testing occurred 24 h later. The data indicate that nicotine (given on training and testing day) enhances trace but not delay cued fear conditioning. No sex differences were found. For delay cued fear conditioning a high level of freezing to the CS was found. Thus, a second experiment examined if the lack of enhancement of delay cued fear conditioning by nicotine was due to a ceiling effect. The CS duration was decreased to 15 s and only one CS-US pairing was used for delay and trace cued fear conditioning. Although overall levels of freezing to the cue were lower in the second experiment, nicotine still enhanced trace fear conditioning but did not enhance delay fear conditioning. Taken together, the results of the present experiments suggest that nicotine enhances hippocampus-dependent versions of fear conditioning.

Analysis of Variance↗

PubMed2004

Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma.

BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor-product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array-based comparative genomic hybridization (CGH). METHODS: Twenty-four samples from the University of California-San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer-amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and ILC were compared. RESULTS: A substantial proportion of the genome was altered in samples of both LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole-arm changes. Smaller regions of gain and loss were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score. CONCLUSIONS: LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma.

Adult↗

PubMed2004

Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients.

The expression of many genes is altered in colon cancer, but the roles of these genes in carcinogenesis are unclear. Using real-time quantitative PCR, we demonstrated that several genes previously implicated in human colon cancer undergo altered expression in the APC(min) mouse adenomatous polyp, a precursor of cancer, as well as in normal-appearing surrounding mucosa. The five genes that were most highly up-regulated in mouse polyp were also significantly up-regulated in polyp-free colon mucosa. Similar changes occurred in morphologically normal mucosa of surgical sections taken from human cancer patients, frequently extending to the margins. Thus, morphologically normal colon mucosa in APC(min) mice and in human cancer patients is not metabolically normal. Altered gene expression in this tissue does not appear to result from a field effect because there was no correlation between extent of altered regulation and distance from polyp or tumor. Our data suggest that alterations of expression levels of these genes may be an early event in carcinogenesis and a marker of risk for the development of colon cancer.

Adenomatous Polyposis Coli↗

PubMed2004

In vitro test of external Qigong.

BACKGROUND: Practitioners of the alternative medical practice 'external Qigong' generally claim the ability to emit or direct "healing energy" to treat patients. We investigated the ability of experienced Qigong practitioners to enhance the healthy growth of cultured human cells in a series of studies, each following a rigorously designed protocol with randomization, blinding and controls for variability. METHODS: Qigong practitioners directed healing intentionality toward normal brain cell cultures in a basic science laboratory. Qigong treatments were delivered for 20 minutes from a minimum distance of 10 centimeters. Cell proliferation was measured by a standard colony-forming efficiency (CFE) assay and a CFE ratio (CFE for treated samples/CFE for sham samples) was the dependent measure for each experiment. RESULTS: During a pilot study (8 experiments), a trend of increased cell proliferation in Qigong-treated samples (CFE Qigong/sham ratios > 1.0) was observed (P = 0.162). In a formal study (28 experiments), a similar trend was observed, with Qigong-treated samples showing on average more colony formation than sham samples (P = 0.036). In a replication study (60 experiments), no significant difference between Qigong-treated samples and sham samples was observed (P = 0.465). CONCLUSION: We observed an apparent increase in the proliferation of cultured cells following external Qigong treatment by practitioners under strictly controlled conditions, but we did not observe this effect in a replication study. These results suggest the need for more controlled and thorough investigation of external Qigong before scientific validation is claimed.

Astrocytes↗

PubMed2004

Temporal gene expression patterns in G93A/SOD1 mouse.

Amyotrophic lateral sclerosis (ALS) is a generally fatal degenerative disorder of motor neurons that has no known cure. Many pathological processes have been implicated. However, the early, initiating events in the disease are poorly understood. We performed multivariate analyses of gene expression of 21 selected genes from categories including glutamate neurotoxicity, oxidative stress, neuroinflammation, aberrant metal ion regulation, apoptosis, and abnormal microglial function on G93A SOD1 mice. These animals develop symptoms of motor neuron dysfunction at about 12 weeks of age, and die at age 18 to 20 weeks. We analyzed animals at both presymptomatic and symptomatic stages. Differential regulation of several genes involved in neuroinflammation, including TNF-alpha, IL- RA, CD86, CD200R and Groalpha, was observed in presymptomatic mice, aged 6-9 weeks, while expression of genes representative of other processes was not altered until the animals reached symptomatic stages. Analysis of expression of inflammatory genes and microglia related genes together also revealed a highly significant change in mutant mice relative to wildtype at 6-9 weeks. These changes were due to the presence of the mutant gene, and not simply to overexpression of a SOD1 gene. These findings are discussed in relation to possible roles of microglia function in the development of ALS.

Age Factors↗

PubMed2004

Biofield perception: a series of pilot studies with cultured human cells.

BACKGROUND: Energy medicine (EM) practitioners often claim to be able to perceive an energetic field associated with the body and to be able to use this skill to diagnose illness and guide treatment strategies. If a biofield associated with cells growing in culture is perceptible to EM practitioners, such an in vitro model would be a useful resource for investigating biofield perception that would provide some unique advantages over clinical models. OBJECTIVE: To evaluate whether EM practitioners can perceive the presence of cultured human cells without visual cues. DESIGN: Three randomized double-blinded pilot studies were used to evaluate the ability of participants to distinguish a flask containing cancer cells growing in culture medium from a flask containing either culture medium or sterile water. Each study consisted of six independent experiments: three with EM practitioners and three with non-practitioners. The number of independent trials for each experiment was estimated by statistical power analyses of the design. Practitioners' feedback from the first two studies was used to revise the protocol for the subsequent studies, with the intent to eliminate potential problems in making this distinction. Labeled flasks ("cells" and "no-cells") were added to serve as references for comparison in the second study and the number of experimental trials was reduced in the third study. SUBJECTS: Eight experienced EM practitioners and nine non-practitioners (laboratory personnel with no EM training). SETTING: A basic science laboratory and office at an academic medical center. OUTCOME MEASURES: In the first 2 studies, we determined the number of correct determinations in a series of 34 trials. In the third study, we determined the number of correct determinations in a series of 10 trials. RESULTS: All participants performed at the level expected by chance. CONCLUSION: While preliminary and inconclusive, these pilot studies found no evidence that EM practitioners can perceive a biofield associated with cancer cells growing in culture.

Clinical Competence↗

PubMed2004

Possible influence of infrasound on glioma cell response to chemotherapy: a pilot study.

OBJECTIVE: To assess the response of cultured human tumor cells to infrasound in combination with conventional anticancer agents using an infrasound-emitting apparatus marketed as a therapeutic device. DESIGN: Two pilot experiments measured proliferation of cultured brain tumor cells exposed to three treatment conditions: infrasound emission alone, infrasound in combination with the chemotherapy 5-fluorouracil (5-FU), and infrasound in combination with ionizing radiation. Results from each experimental condition were compared to those from appropriate control conditions. OUTCOME MEASURE: A standard colony-forming efficiency assay was used to assess tumor cell proliferation. RESULTS: Tumor cell proliferation was not significantly altered by treatment with infrasound alone, nor did infrasound appear to influence cellular response to x-rays. There was a significant interaction between 5-FU and infrasound (P < 0.0001), however, evident in decreased colony formation. CONCLUSION: Further research is warranted to assess potential synergism between infrasound and 5-FU against tumor cell proliferation, and to investigate the possible therapeutic use of infrasound.

Antimetabolites, Antineoplastic↗

PubMed2004

Mammary tumor heterogeneity in wt-ErbB-2 transgenic mice.

Phenotypic and biological heterogeneity was studied in a single transgenic mouse model to determine the level of biological variance. We analyzed 1,258 tumors from 417 MMTV-wt-ErbB-2 transgenic mice, subdivided by casein or soy-based dietary randomization and hormonal treatment. Variance in tumor histologic features, growth pattern, invasion, metastases, and multi-focality were detected in untreated and treated mice. Ninety-three percent (1,174/1,258) of tumors had the solid growth pattern widely reported in this model. However, among the solid tumors, a spectrum of growth patterns, from well-circumscribed tumors with a pseudocapsule to locally invasive or highly aggressive, metastatic subtype, was observed. Of the non-solid tumors, glandular features were prominent in 84 (7%). Adenocarcinomas included papillary, acinar/glandular, and adenosquamous subtypes. Adenosquamous tumors were exclusively observed in the group of mice treated on a short-term basis with estrogen. In contrast to the reported literature for this transgenic mouse model, mammary tumors were multifocal in the majority of cases (303 of 417 mice, or 73%). Results of this extensive study of a single transgenic model of mammary tumorigenesis indicate phenotypic and biological heterogeneity not previously associated with this transgenic mouse. These data support a complex, multistep process of carcinogenesis and clonal evolution, with biological and phenotypic variance similar to that observed in human mammary cancer development.

Adenocarcinoma↗