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C Harris

Publications and source records attributed to C Harris.

At least 91 records · Page 5Linked to original sources
PubMed1997

HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas.

PURPOSE: The HER-2/neu gene codes for a membrane receptor protein that is homologous, but distinct from the epidermal growth factor receptor. This investigation was performed to validate fluorescence in situ hybridization (FISH) as a sensitive and specific method for assessing HER-2/neu gene amplification in archival tissue and to test whether this alteration is associated with poor prognosis. MATERIALS AND METHODS: HER-2/neu gene amplification was determined by FISH in 140 archival breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node-negative breast cancers was assessed for amplification by FISH to determine the utility of HER-2/neu gene amplification. RESULTS: Relative to solid-matrix blotting procedures, FISH analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers. Among patients treated by surgery only, the relative risks (relative hazard) of early recurrence (recurrent disease within 24 months of diagnosis), recurrent disease (at any time), and disease-related death were statistically significantly associated with amplification. The prognostic information contributed by HER-2/neu amplification was independent of the other markers studied. CONCLUSION: FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification in the absence of adjuvant therapy is an independent predictor of poor clinical outcome and is a stronger discriminant than tumor size. Women with small tumors that had gene amplification were at increased risk of recurrence and disease-related death.

Aged↗
PubMed1997

Oral and dental health in alcohol misusing patients.

Dental and oral health and their relationship to nutritional status among a group of alcohol misusers (n = 107) from south London is reported. The Alcohol Use Disorders Identification Test (AUDIT) questionnaire was validated as an accurate and reliable screening questionnaire for use in alcohol misuse detection by a dentist. Half of the study population consumed >200 units of alcohol/week, and 80% were heavy smokers. A high incidence of tooth wear and trauma to the dentition was recorded. Eight subjects had oral mucosal lesions, including two previously treated carcinomas. The dental health in alcoholics overall was not compromised, but nutritional impairment (body mass index and reduced midarm muscle circumference) was associated with periodontal lesions. Oral mucosal health of alcoholics is of concern, particularly in heavy smokers. The interrelationships between dental-oral health and alcohol-tobacco usage have implications for preventative counseling in this patient group.

Adult↗
PubMed1996

Use of fluorescent in situ hybridization to detect aneuploidy in cervical dysplasia.

Fluorescent in situ hybridization (FISH) with alpha satellite DNA probes for chromosomes 11 and X were applied to normal, atypical, and dysplastic cervical-vaginal cytology smears to evaluate the detection of hyperploidy in suspected abnormal cells. Forty-six cases were obtained from fixed archival material. Eight cases with a morphological diagnosis of within normal limits (WNL) were directly selected to use as controls. The other 38 cases were blinded as study cases. These included five WNL, six ASCUS, six SIL-LG, 16 SIL-HG, four invasive squamous cell carcinomas, and one case of adenocarcinoma of the cervix. Cells with chromosome copy numbers suggesting hyperploidy (3-4 signals per chromosome specific probe) were found more often in higher grade dysplasia (Bethesda class SIL-HG) cases and less often in lower grade lesions (SIL-LG). All cases morphologically diagnosed as WNL were found to have normal copy number except for one control case which was hyperploid and, upon reexamination of the original slides, was upgraded from normal to atypical squamous cells of undetermined significance (ASCUS). Our FISH results are similar to those of previous studies involving flow cytometry and morphometric cytometry in which changes in ploidy correlated with progression toward higher grade lesions. However, FISH with enumeration probes offers a higher resolution view of the genome than is possible with flow cytometry or morphometry by allowing detection of specific chromosome changes in small numbers of affected cells in a routine cervical smear, and it may have the capacity to detect those cases in which progression toward high grade dysplasias is more likely.

Adenocarcinoma↗
PubMed1996

Balanced interaction of growth factors and taurine regulate energy metabolism, neuronal survival, and function of cultured mouse cerebellar cells under depolarizing conditions.

The development of neuronal cells in a given cellular environment requires mechanisms that dynamically regulate the balanced interactions of multiple factors which are known to control maintenance and plasticity in function of neurons throughout constantly changing extracellular conditions. Periodic release of excitatory amino acids from both developing glial and neuronal cells into the extracellular environment and their uptake has been shown to stimulate neuronal function in concert with growth factors that control the degree of depolarization and, therefore, neuronal function. This study attempts to characterize the critical concentrations of these factors either alone or together in relation to energy metabolism, cell survival and function. We demonstrate a close correlation between energy metabolism of neuronal cells, controlled by the combination of growth-factors (beta FGF, BDNF), and glutamate-taurine as well as K+ in depolarizing concentrations (10-25 mM), during the balancing act of neuronal survival or death, and neuronal function. These functions depend on medium conditions (energy sources, ion composition), the ratio of glial cells versus neurons and cell density. Granule cell migration as a measure of developmental neuronal function was analyzed in the presence of various combinations of growth factors and taurine under various depolarizing conditions (glutamate, K+). We found that K+ concentrations > 7 mM in BME and 10% horse serum blocked migration in less than 30 min. Taurine did not prevent this effect. However, in the presence of HEPES as well as in F12-medium with HEPES, taurine restored granule cell migration. On the other hand, glutamate-or NMDA-mediated depolarization stopped migrating granule cells while NMDA antagonists extended the period of migration. Taurine amplified the stop-signal in the presence of glutamate agonists but increased the number of migrating cells in the absence of glutamate. Thus, the mechanisms of glutamate receptor mediated excitotoxicity, possibly by reducing Ca2+ influx under depolarizing conditions, but amplifies the stop-signal, Ca2+ levels may not control granule cell migration.

2-Amino-5-phosphonovalerate↗
PubMed1996

The molecular identity of Ca channel alpha 1-subunits expressed in rat sympathetic neurons.

Much of our understanding of the mechanisms of the gating, modulation, and function of neuronal Ca channels has its origins in investigations of sympathetic neurons. In this article, we use molecular analyses to identify the three Ca channel alpha 1-subunits that are the likely counterparts to the pharmacologically defined: omega-Conotoxin GVIA-sensitive N-type; dihydropyridine-sensitive L-type, and omega-Conotoxin GVIA-insensitive, dihydropyridine-insensitive Ca channel currents observed in sympathetic neurons. With a combination of degenerate and exact primers, small regions of Ca channel alpha 1-subunit sequences were amplified by the polymerase chain reaction (PCR). Although all five Ca channel alpha 1-subunit genes were expressed in rat sympathetic ganglia, alpha 1B-, alpha 1D-, and alpha 1E-derived cDNAs were the dominant species. No novel Ca channel alpha 1-sequences were identified in the regions selected for amplification, and we conclude that alpha 1B, alpha 1D, and alpha 1E likely encode, respectively, N-type, L-type, and non-N/non-L-type channel currents of rat sympathetic neurons. In addition, we show that Ca channel beta 2-, beta 3-, and beta 4-subunit sequences are strongly represented in sympathetic ganglia. The results of this study also suggest that alpha 1D, and not alpha 1C, regulates Ca influx through dihydropyridine-sensitive Ca channel currents.

Amino Acid Sequence↗
PubMed1996

Outpatient management of diabetes mellitus in five Arizona Medicare managed care plans.

We report findings on the outpatient management of diabetes mellitus in Medicare beneficiaries enrolled in five Arizona Medicare-managed care plans. These findings are the baseline of an ongoing collaboration between the Health Services Advisory Group, Inc., Arizona's Peer Review Organization (PRO), and the five plans whose object is improved care of diabetes patients. The purpose of the study was to determine congruity between quality indicators identified by the five plans and the care actually received by diabetes patients enrolled in the five plans. The five plans agreed on a common set of quality indicators, including 10 services and 10 measures of patient status. Each plan has identified its diabetic population, 75 of whom are randomly selected each quarter by the PRO for chart review and inclusion in the study. The findings in this report cover two quarters of data. Data from chart review were examined to determine the extent to which actual practice reflected the indicators. The mean patient age was 71.8, and for most patients onset occurred between 55 and 69 years of age. About 25% had a positive family history, and we estimate the annual incidence of diabetes in this population to be about 1.1%. Mean hemoglobin A1c (HbA1c) was 8.9 +/- 2.1%; 46% were hypertensive; 42% continued to smoke cigarettes; 36% had retinopathy; 20% had proteinuria; and only 22% were on some kind of exercise program. Thirty-two percent were hospitalized during the 1-year baseline period, and the average number of outpatient visits per patient was 11.1 +/- 7.4. When care provided to diabetes patients enrolled in the plans was compared with the 10 quality standards identified by the plans themselves, only two of these standards was attained in more than 60% of patients: blood pressure, 98.7%; and foot examination, 62.7%. Two standards were achieved less than one-third of the time: urine dipstick, 10.4%, and appropriate use of angiotensin-converting enzyme (ACE) inhibitors, 31.25%. The others were all between 40 and 55%. Of the 10 service standards, about one-third received 1-4, one-third received 5-6, and one-third received 7-10. Only 5% of patients received 9 or 10 services. Outpatient management of diabetes patients in managed-care plans is similar to that in fee-for-service. When compared with fee-for-service or another HMO, a higher proportion of Arizona-managed care patients had HbA1c, and a much lower proportion had a dipstick test for urine protein. Values for other variables were usually within 10 percentage points of each other. Regardless of payment scheme, diabetes care is characterized by inconsistencies, omissions, and a lower than desirable level of services. Although few patients received most of the indicator services, diabetes patients are nevertheless high utilizers of medical care, both in and out of the hospital. The hospitalization rate is twice that of Arizona Medicare beneficiaries as a whole, and the number of office visits is three or four times that reported in other studies. Further, it seems that many visits are required to achieve even these modest service levels. Had the average number of visits been six or less, HbA1c rates, for example, would have fallen to less than one-third in three of the five plans. We believe that these data are conservative because it is likely that some and perhaps most of these indicators are underreported. It should be emphasized that these are baseline data whose purpose is to provide a basis against which subsequent improvements many be measured.

Aged↗
PubMed1996

Allergy testing.

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Humans↗
PubMed1996

A top-down approach to whole genome visualization.

The investigation of large DNA contigs like complete chromosomes or genomes requires novel methods of data visualization. The complex information contained in a genome, particularly the relation of its individual genetic elements, needs to be accessible in a comprehensive, intelligent and intelligible manner. The yeast genome is expected to contain more than 6,000 Open Reading Frames (ORFs). As yet, the function of many of these ORFs has not been characterized satisfactorily. Also, many ORFs are found to have redundant copies elsewhere in the genome that originated from common ancestors. Other genetic elements (e.g. Tss, delta-elements, t-RNAs) are present in multiple copies. To visualize these relationships, a top-down "genome browser" is introduced that enables inspection of genomic data at different levels of abstraction (e.g. chromosomes, coding/non-coding regions, high/low levels of similarity). This novel tool is a key component for the integrated services approach to biological sequence data management (Heumann et al. 1995) and is accessible through the world wide web (WWW). This work demonstrates how the genome browser visualizes the results of an all-against-all comparison of the elements in the yeast genome as a graph. Interactive navigational queries across yeast chromosomes along the lines of sequence similarity open versatile options for the detailed investigation of genome properties. For sequence comparison the hashed position tree HPT (Mewes & Heumann 1995) is applied. Sequence similarity relationships are represented using the genome similarity graph (GSG) (Heumann & Mewes 1996c).

Chromosomes, Fungal↗
PubMed1996

Needle exchange.

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HIV Infections↗
PubMed1995

Agouti structure and function: characterization of a potent alpha-melanocyte stimulating hormone receptor antagonist.

The murine agouti gene encodes for a novel 131 amino acid protein. The sequence includes a 22 residue putative secretion signal, an internal basic region, and a C-terminal domain containing 10 cysteines. Agouti has been found to antagonize the binding of certain pro-opiomelanocortin peptides, such as alpha-melanocyte stimulating hormone (alpha-MSH), to the murine melanocortin-1 receptor (MC1-R). We report the purification of a secreted murine agouti to homogeneity by a two-step procedure from baculovirus-infected Trichoplusia ni (T. ni). The protein is glycosylated and exhibits competitive, high-affinity antagonism (Ki = 0.8 nM) versus alpha-MSH in cell-based assays employing B16F10 cells. Association state analysis by analytical ultracentrifugation reveals that agouti exists in a monomer--dimer plus aggregate equilibrium at low micromolar concentrations. Data from secondary structure studies indicate that the protein is highly stable to thermal denaturation. Enzymatic digestion to probe disulfide bond arrangement yielded a discrete C-terminal (Val 83-Cys 131) domain. The isolated highly cysteine-rich C-terminal domain retains alpha-MSH antagonism equipotent with mature agouti. This bioactive domain contains all 10 cysteines which exhibit sequence homology when aligned with several conotoxins.

Agouti Signaling Protein↗
PubMed1995

Four new cases of inverted terminal duplication: a modified hypothesis of mechanism of origin.

We present 4 recently diagnosed cases of inverted tandem duplication with involvement of the respective terminal band. Based on these 4 cases and review of the literature, the term "inverted terminal duplication" is proposed to designate specifically the type of inverted tandem duplication which involves the terminal band. A modification of the previous hypothesis of mechanism of origin is advanced. It is speculated further that a telomeric deletion of a meiotic chromosome followed by a U-type reunion of the chromatids, considered to be the first steps of the proposed mechanism of origin, may not be a rare gonadal event.

Abnormalities, Multiple↗
PubMed1995

Inhibition of aberrant crypt growth by non-steroidal anti-inflammatory agents and differentiation agents in the rat colon.

Aberrant crypts are aggregates of single to multiple colonic crypts evidencing hallmarks of dysplasia and may be the earliest detectable pathological lesions for colon cancer. The aberrant crypt assay has been developed in 2 protocols. In one, putative chemoprevention agents are tested for inhibitory effects when administered concomitantly with a carcinogen. In the other, the objective of this study, aberrant crypts were induced in F344 rats by parenteral injection of the colon carcinogen azoxymethane (AOM) and allowed to develop for 4 weeks, when an average of 90-100 aberrant crypt foci per colon were found in the methylene blue-stained colon. Then, during the second 4 weeks of the experiment, aberrant crypts were allowed to further develop to a frequency of > 150 foci per colon, a time when multi-crypt foci were observed. During this time we tested the inhibitory effects of 4 analgesic drugs and 2 differentiation agents for effects of aberrant crypt growth and development. We found the non-steroidal anti-inflammatory drugs piroxicam, aspirin and ibuprofen, but not acetaminophen, to be effective in suppressing aberrant crypt formation or the progression to foci of multiple aberrant crypts. Treatment with chemosuppressing agents 13-cis-retinoic acid (13-cRA) and 4-hydroxyphenretinamide (4-HPR), known differentiating agents, however, did suppress expansion of aberrant crypt foci, with 13-cRA being the much more potent agent.

Acetaminophen↗
PubMed1995

Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T.

We performed proton magnetic resonance spectroscopic imaging (MRSI) at high magnetic field (4.1 T) to study N-acetylaspartate, creatine, and choline levels in the brains of normal control subjects and patients with intractable temporal lobe epilepsy. We compared the results of MRSI to those of other presurgical techniques to determine the sensitivity of this method in the lateralization of the epileptic focus. The normal hippocampal creatine-N-acetylaspartate ratio was 0.71 +/- 0.14 with no differences between left and right. Using the mean control hippocampal creatine-N-acetylaspartate ratio plus 2 standard deviations to identify statistically significant changes, we found lateralizing metabolic abnormalities corresponding to the operated temporal lobe in all patients. Four patients (40%) had contralateral abnormalities, and 2 of them had bilateral independent seizure onset confirmed by intracranial electroencephalographic studies. Statistically significant increases in the choline-N-acetylaspartate ratio in comparison to healthy volunteers were observed in 8 of the 10 patients. With the creatine-N-acetylaspartate ratio, MRSI demonstrated a 100% sensitivity compared to magnetic resonance imaging, which identified pathology in 70% of the patients. These findings suggest that proton MRSI yields a distinctive metabolic profile in patients with temporal lobe epilepsy and is sensitive in detecting bilateral metabolic abnormalities in some patients. These preliminary findings suggest that MRSI is more sensitive than magnetic resonance imaging in the lateralization of epileptic foci in temporal lobe epilepsy.

Adult↗
PubMed1995

Risk-adjusted analysis of surgeon performance: a 1-year study.

A 1-year prospective analysis was undertaken of all non-day-case general surgery in a district general hospital. Using the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) scoring system 3004 patients were assessed. From the predictions of mortality and morbidity so obtained, a quality measure, the ratio of observed to expected numbers of deaths and complications (O:E ratio) was determined for each surgeon, both overall and within specialty zones. The present study demonstrates the serious hazard in using 'raw' uncorrected mortality and morbidity statistics to compare surgeon performance. Mortality rates varied from 1.0 to 4.9 per cent whereas O:E ratios ranged from 0.83 to 1.06; morbidity rates varied from 5.3 to 12.6 per cent with O:E ratios 0.86-1.02. Great misunderstanding may result from the publication of surgeon or hospital 'league tables'. The present study demonstrates a technique that might allow surgeon performance to be monitored adequately and accurately.

Day Care, Medical↗