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Biomedical subjects

D Moore

Publications and source records attributed to D Moore.

At least 163 records · Page 9Linked to original sources
PubMed1994

Epidermal-growth-factor-receptor expression is associated with rapid tumor proliferation in bladder cancer.

Epidermal-growth-factor-receptor (EGF-r) expression has been proposed as a prognostic marker in bladder cancer and is associated with rapid proliferation in cell lines. Ninety-three fresh and 74 formalin-fixed bladder tumors were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry to assess the relationship between EGF-r expression and proliferation as well as the prevalence of epidermal-growth-factor-receptor (EGF-r) gene amplification. EGF-r expression was strongly associated with BUdr labeling index, grade and stage. EGF-r expression emerged as a stronger predictor of tumor proliferation than grade or stage in analysis of variance. Rapid tumor proliferation might be responsible for bad prognosis reported in EGF-r positive bladder tumors. Also chromosome 7 copy number was associated with grade and stage. EGF-r gene amplification was uncommon (5 of 107 tumors). However, FISH analysis allowed characterization of the pattern of amplification, with clustering of signals suggestive of intrachromosomal amplification more common than diffuse distribution consistent with extrachromosomal amplification.

Bromodeoxyuridine↗
PubMed1994

Preliminary crystallographic studies on human complement pro-factor D.

The recombinant zymogen of the human complement protein factor D has been crystallized. Crystals were grown by vapor diffusion using polyethylene glycol 6000 as precipitant. Two crystal forms obtained at pH 5.4 belong to space group P2(1). The crystals grow to dimensions of 0.6 mm x 0.3 mm x 0.3 mm in three days, are stable in the X-ray beam, and diffract to 2.4 A.

Amino Acid Sequence↗
PubMed1994

Structure of human factor D. A complement system protein at 2.0 A resolution.

Factor D, an essential enzyme for the activation of the alternative pathway of the complement system, belongs to the serine protease superfamily. The crystal structure of the enzyme was solved by a combination of multiple isomorphous replacement and molecular replacement methods. The present model was refined to an R-factor of 18.8% using 23,681 observed reflections between 7.5 and 2.0 A resolution, with a root-mean-square deviation from standard bond lengths of 0.016 A. The two non-crystallographically related molecules in the triclinic unit cell have distinctive active site conformations. The protein has the general structural fold of a serine protease, but there are several unique amino acid substitutions resulting in significant alterations in the critical loops responsible for catalysis and substrate specificity in serine proteases. Factor D is the first complement serine protease whose three-dimensional structure has been determined.

Amino Acid Sequence↗
PubMed1994

Nucleotide sequence of the P1 region of serotype Asia1 foot-and-mouth disease virus.

Differences in the amino acid sequence of foot-and-mouth disease virus (FMDV) virion proteins (VP) among the various FMDV serotypes, particularly in the VP1 polypeptide, are the basis for antigenic diversity of this virus group. This phenomenon provides the basis for type diagnosis of FMDV by the polymerase chain reaction (PCR). In order to specifically identify the Asia1 FMDV serotype by PCR, the nucleotide sequence of its P1-coding region was determined. The sequence exhibited over 70% homology with the P1 gene segment of type O1k. The deduced amino acid sequence shares 79% homology with that of the P1 region of serotype O1k.

Amino Acid Sequence↗
PubMed1994

Brain choline in depression: in vivo detection of potential pharmacodynamic effects of antidepressant therapy using hydrogen localized spectroscopy.

1. Seven subjects with depression and matched controls were studied using proton spectroscopy to test the hypothesis that choline will be elevated in depression. 2. The proton spectroscopy was repeated after recovery from depression. 3. The study confirmed a state dependent increase in choline in the brain. 4. This change may be used as an in vivo marker of change in depression.

Aged↗
PubMed1994

Contributions of working memory and evaluation and regulation of understanding to adults' recall of texts.

We examined evaluation and regulation in adults and the relative contributions of working memory, components of working memory (storage and processing efficiency), and evaluation and regulation to text recall. Younger and older adults' sentence reading times, sentence rereadings, and memory for texts containing inconsistent information were assessed in an on-line analysis. Older adults detected inconsistent information during reading but failed to selectively regulate understanding by rereading problematic information. Failure to regulate understanding was related to poorer memory for problematic information, overall text recall, and ability to report text inconsistencies. Age differences in selective rereading were substantially reduced when processing efficiency was controlled, and age-related variance in passage recall was substantially reduced when differences in processing efficiency and selective rereading were controlled. Results indicate that processing efficiency and selective rereading contribute to adult age differences in text recall, and highlight the importance of distinguishing between a global strategy of rereading and selective rereading in response to comprehension problems.

Adult↗
PubMed1994

Gravitational biology of mushrooms: a flow-chart approach to characterising processes and mechanisms.

Flow charts are presented which systematise recently published work on gravitropic responses of the mushroom stipe of Coprinus cinereus. The hypothetical model represented by the charts suggests that the meiotic division is a pivotal point in the gravitational biology of the mushroom fruit body. The unilateral gravity vector seems to be required for formation of the tissues in which meiosis normally occurs, and stipes become gravitropically competent only after onset of meiosis. The gravitropism flow-chart also indicates that two signals emanate from the upper regions of the stipe, one promotes the process of gravitropic bending, and is followed by a second signal which compensates for excess bending and adjusts the stipe apex to the vertical. Formalisation of the various observations into flow-charts, even though comparatively simple at the moment, facilitates comparison with other species and concentrates attention on aspects requiring further experimental analysis.

Calcium↗
PubMed1994

Kinetics of stipe gravitropism in the mushroom fungus Coprinus cinereus under the conditions of microgravity simulation provided by clinostat treatment.

The extent of the gravitropic response, measured as the angle of the stipe apex at maximum curvature, was dependent upon the gravitational exposure time. The reaction time did not depend on exposure time, and interruption of gravitational exposure by a period of clinostating allowed the gravitational stimulus to decay. It is concluded that the gravitropic impulse is an 'all-or-nothing' signal in Coprinus cinereus, that perception and response probably occur in the same tissue regions, and that sustained exposure to the unidirectional gravity vector is necessary for the normal gravitropic response. The presentation time was found to be 7 min. Immediately after reaching curvature, stipes placed on the clinostat after various gravity exposure times 'relaxed' by 5 degrees. This relaxation suggests that gravitropic bending is a two-stage process with an initial, reversible, phase of plastic bending followed by a 'fixation' phase providing the gravitropic stimulus has been maintained.

Coprinus↗
PubMed1994

High concentrations of mannitol in the shiitake mushroom Lentinula edodes.

A quantitative analysis of mannitol, using gas-liquid chromatography (GLC), was carried out in the various tissues of Lentinula edodes (Berk.) Pegler in comparison with Agaricus bisporus (Lge) Imb. and Coprinus cinereus (Schaeff.: Fr.) S. F. Gray. Mycelia of L. edodes had a low level of mannitol (ca 1% on a dry wt basis) compared with the fruit body stipe and pileus (20-30%). The highest level of mannitol was observed in the pileus of A. bisporus (close to 50%). These observations of similar levels of accumulation of mannitol suggest that glucose catabolism in L. edodes and A. bisporus are similar. No mannitol was detectable in the pileus of C. cinereus.

Agaricus↗
PubMed1994

Pathogenesis of pulmonary fibrosis: platelet-derived growth factor precedes structural alterations in the Hermansky-Pudlak syndrome.

Peptides that modulate mesenchymal cell function have been detected in the fibrotic lung disorders once physiologic dysfunction is present. Despite this close association with manifest disease, their role in initiating alveolar remodeling remains unknown. We examined the hypothesis that one potent peptide, platelet-derived growth factor (PDGF), would be present at the alveolar surface before the onset of physiologic dysfunction in patients in whom pulmonary fibrosis subsequently develops. Bronchoalveolar lavage and physiologic assessment were performed in asymptomatic patients with the Hermansky-Pudlak syndrome (n = 30), obligate heterozygous (n = 9), and normal volunteers (control group). Lavage cell number and profile were normal, but alveolar macrophages demonstrated characteristic autofluorescence and ultrastructural features of ceroid. Lavage fluid from physiologically normal patients with Hermansky-Pudlak syndrome and from those with occult restrictive disease demonstrated two PDGF-related peptides (14 kd and 38 kd). Radioligand binding and fibroblast proliferation assay demonstrated that the peptides were functional. By immunoassay the concentration of PDGF in lavage fluid was six times greater than control values (p < 0.01). In situ hybridization together with bioassay indicated that alveolar macrophages were one cellular source of PDGF. Similar results were obtained for heterozygotes. These data identify macrophage-derived PDGF peptides as important candidate molecules in the initiation of alveolar remodeling in the fibrotic lung disorders.

Adolescent↗
PubMed1994

Electrodiagnosis of upper limb weakness in acute quadriplegia.

Clinical and neuropathologic observations after cervical spinal cord injury suggest varying involvement of gray and white matter. The resulting upper limb weakness may reflect varying degrees of upper motoneuron (UMN) and/or lower motoneuron (LMN) involvement. This study uses electrophysiologic measures, including compound muscle action potential (M response) amplitude, root mean square (RMS) of the surface electromyographic activity during voluntary muscle contractions and the firing rate of motor units, to distinguish UMN and LMN weakness in upper extremities after acute quadriplegia. M response amplitude did not correlate with strength; many muscles had large M responses given their strength. These muscles manifest: (1) high M/RMS ratios (ratio of electrically elicited to voluntarily recruited electromyographic activity) and (2) slow firing rates of single motor units during maximal isometric contractions. For muscles with normal M amplitudes, M/RMS ratio correlates inversely with strength. For muscles with normal M/RMS ratios, M amplitude correlates positively with strength. Cluster analysis was used to distinguish UMN, LMN or Mixed types of weakness. Distinguishing these different types of weakness in acute quadriplegia may allow individualized rehabilitation for the type of weakness present.

Action Potentials↗
PubMed1994

Transposition of the imidazole ring substituents of angiotensin mimetics related to Losartan.

A series of analogues related to Losartan in which the imidazole ring substituents were transposed have been prepared. Biological evaluation, both in vitro and in vivo, demonstrated that the orientation of the imidazole ring has a subtle yet significant effect upon the potency of these analogues. This information has provided an insight into the possible mode of receptor binding of Losartan and related compounds.

Angiotensin Receptor Antagonists↗
PubMed1993

Cyclic postural behavior in the crayfish, Procambarus clarkii: properties of the pattern-initiating network.

Crayfish exhibit complex cyclical adjustments in abdominal posture during certain forms of backward walking. An isolated nerve cord preparation was used to investigate the properties of the interneurons which direct this alternation of abdominal flexion and extension. The command function for this cyclic postural behavior appears to be the domain of a distributed network of multiple pattern-initiating interneurons: each interneuron may be viewed as a command element within a command system. The cyclic pattern may be elicited by stimulation of small axon bundles pulled from the ventrolateral margins of any of the abdominal connectives. As few as one stimulus pulse to the axon bundle can elicit a single cycle of patterned output, although more pulses are generally necessary. This suggests some convergence or amplification step in the pattern-initiating interneurons. The amplification may be accomplished by several pattern-initiating interneurons that are coupled to one another and converge on pattern generating circuits in each ganglion. Evidence supporting this interpretation is presented. Experiments involving resection of the cord reveal that the pattern-initiating signals transfer laterally across all of the abdominal ganglia, but the network contains a bias for descending signal conduction once a lateral transfer is made. This finding agrees with other results. For example, recordings from pattern-initiating axon bundles at rostral and caudal locations in the abdominal nerve cord show several descending but only one ascending unit activated during cyclic pattern generation. We also show that an isolated ganglion is capable of producing the cyclic motor program, although the outputs are much weaker than those elicited in the intact abdominal cord. Therefore, the pattern-initiating system is both central and distributed.

Abdomen↗
PubMed1993

Insulin-like growth factor-I receptors are overexpressed and predict a low risk in human breast cancer.

IGF-I receptor (IGFR) content and its prognostic significance were evaluated in human breast cancer specimens using a sensitive and specific radioimmunoassay (V. Pezzino et al., Metabolism, 40: 861, 1991). The prognostic significance of IGFR expression was investigated by two different approaches: (a) detectable IGFR content was measured in 82% of specimens in a consecutive series of 184 human breast cancers and in 32% of 19 normal breast tissues. The average IGFR content in breast cancer was nearly 10-fold higher than the value observed in normal breast tissue (7.6 +/- 0.8 versus 0.8 +/- 0.1 ng/0.1 mg protein, mean +/- SEM; P < 0.001). IGFR content was positively correlated with estrogen (ER) and insulin receptor content (r = 0.269 and 0.515, respectively, Pearson correlation) but not with progesterone receptors (PR). No significant correlation was observed between IGFR content and a variety of tumor parameters (tumor size, lymph node involvement, grade) and host characteristics (age, body mass index, menopausal status); (b) IGFR content was measured in a noncontinuous series of 265 primary breast cancer specimens subdivided into 136 high-risk and 129 low-risk specimens on the basis of being either negative (ER-/PR-/aneuploid/high S-phase) or positive (ER+/PR+/diploid/low S-phase) for four well-established prognostic factors. IGFR levels were significantly higher in the low-risk group (6.4 +/- 0.4 ng/0.1 mg protein, mean +/- SEM) than in the high-risk group (3.6 +/- 0.5; P < 0.0001, Wilcoxon sum rank test). In summary, our data indicate that there is an elevated IGFR content in most human breast cancers compared with normal breast tissue and that an elevated IGFR content is a favorable prognostic indicator.

Adult↗
PubMed1993

Lead poisoning among low-income children in Orange County, California. A need for regionally differentiated policy.

OBJECTIVE: To estimate the prevalence of elevated lead levels among children in Orange County, California, and to evaluate the appropriateness of a universal pediatric blood lead screening policy in this community. DESIGN: Venous blood lead testing was conducted and results were analyzed according to seven blood lead strata ranging from less than 0.50 mumol/L (10 micrograms/dL) to 3.35 mumol/L (70 micrograms/dL) or higher. A cost analysis of the lead-testing program in Orange County was conducted. SETTING: Children meeting poverty eligibility criteria and attending the Child Health and Disability Prevention Program, the state's implementation of the federal Early and Periodic Screening, Diagnosis and Treatment (EPSDT) services program. PARTICIPANTS: A total of 5115 Orange County children between 12 and 72 months of age using EPSDT services from March through December 1992. MAIN OUTCOME MEASURES: Blood lead levels and associated costs of the testing program stratified by level of blood lead elevation. RESULTS: Blood lead levels of 0.50 mumol/L (10 micrograms/dL) or higher were found in 371 children (7.25%; 95% confidence interval, 6.66% to 7.85%), but only six children (0.12%; 95% confidence interval, 0.04% to 0.20%) had elevations greater than 1.20 mumol/L (25 micrograms/dL). Five children (83.3%) had histories of lead consumption unrelated to ingestion of lead-containing paint but related to the use of lead-containing folk remedies and cooking utensils. Costs for detection of children with blood levels elevated to 0.50 mumol/L (10 micrograms/dL) or higher was $310 per child and for levels of 1.20 mumol/L (25 micrograms/dL) or higher was $19,139 per child. CONCLUSIONS: These data suggest that lead poisoning is not a major public health problem among Orange County children and detection of infrequent cases would involve a high cost per child. In jurisdictions with newer housing, initial screening for a history of possible lead exposure alone may offer reasonable efficacy that is cost-effective. The scope of lead-testing programs should be determined according to local needs and conditions.

California↗
PubMed1993

Thallium poisoning. Diagnosis may be elusive but alopecia is the clue.

Thallium is a heavy metal whose salts are used in some rodent poisons and in the manufacture of optical lenses, semiconductors, scintillation counters, low temperature thermometers, and switching devices, green coloured fireworks, and imitation jewelery, and as chemical catalysts. In clinical practice thallium isotopes are used in cardiac scanning, but the use of thallium salts to treat scalp ringworm was abandoned earlier this century because of their toxicity. The sale of thallium in Britain is strictly licensed because of its toxicity and potential for use in murder, which is helped by the fact that thallous salts are colourless, tasteless, and odorless. The more water soluble salts (such as thallium sulphate, acetate, or carbonate) have higher toxicity, and although the toxic dose is variable most deaths occur after the ingestion of 10-15 mg/kg of soluble salt. Most cases of thallium toxicity occur after oral ingestion but severe toxicity has been reported after inhalation of contaminated dust from pyrite burners, in zinc and lead smelting, and in the manufacture of cadmium, after dermal absorption through protective rubber gloves, and after snorting what was thought to be cocaine. The elimination half time of thallium is between 1.7 and 30 days depending on the time since, and chronicity of, ingestion. The elimination time phases are apparent and because of the long terminal elimination half time thallium may act as a cumulative poison. We present two cases of thallium poisoning with intent to kill.

Adult↗
PubMed1993

Heterogeneity of erbB-2 gene amplification in bladder cancer.

erbB-2 amplification and overexpression have been suggested as potentially useful prognostic markers in bladder cancer. We examined 141 bladder tumor specimens (45 fresh tissue samples and 96 formalin fixed tissue blocks) for erbB-2 amplification using fluorescence in situ hybridization. A dual labeling hybridization using a repetitive pericentromeric probe specific for chromosome 17 and a cosmid probe for the erbB-2 locus was performed to analyze the erbB-2 copy number in relation to chromosome 17 copy number on a cell by cell basis. Amplification (more than twice as many erbB-2 signals as centromere 17 signals per tumor) was found in 10 of 141 tumors. There was considerable heterogeneity in erbB-2 amplification. In a given tumor there was a wide range of erbB-2 copy number in amplified cells. The arrangement of erbB-2 signals in clusters in all amplified cases suggests that erbB-2 amplification occurs intrachromosomally in bladder cancer. Amplification was found only in tumors with aneusomy of chromosome 17 and was more frequent in pT2-T4 tumors than in pTa/T1 tumors. Overexpression was present without amplification in 51 tumors. All tumors with erbB-2 amplification showed erbB-2 overexpression. However, in 5 samples the proportion of cells with amplification was significantly lower than the fraction of cells with overexpression, indicating coexistence of two different mechanisms leading to overexpression in these tumors.

Bromodeoxyuridine↗