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Biomedical subjects

C M Moore

Publications and source records attributed to C M Moore.

At least 19 recordsLinked to original sources

Effects of myo-inositol ingestion on human brain myo-inositol levels: a proton magnetic resonance spectroscopic imaging study.

BACKGROUND: Cerebrospinal fluid levels of myo-Inositol (m-Ino) are reported to be decreased in patients with affective disorder, and dietary supplements of m-Ino have been shown to reduce the symptoms of major depression. Myo-Inositol transport across the blood-brain barrier is mediated by a low capacity, saturable system. This study tests whether dietary m-Ino increases brain m-Ino or changes brain metabolism of m-Ino, possibly explaining the ability of this compound to alter mood. METHODS: Using proton magnetic resonance spectroscopic imaging, we measured m-Ino levels in occipital gray and parietal white matter of seventeen healthy subjects. Magnetic resonance spectroscopic imaging was performed twice at baseline as well as at day 4 and day 8 while subjects ingested 6 g of m-Ino twice a day. RESULTS: Following 4 days of m-Ino, m-Ino/Cr was 20% higher than baseline levels in occipital gray matter (p < 0.04) and 8% higher in parietal white matter (p = ns). By day 8, m-Ino/Cr ratios had returned to baseline values. CONCLUSIONS: Brain m-Ino levels initially increase during m-Ino administration and subsequently return to baseline levels. The time-limited increases observed for brain m-Ino may reflect homeostatic mechanisms, possibly associated with the role of m-Ino as a cerebral osmolyte, or with changes in brain phosphoinositide metabolism.

Adult

Determination of phenethylamine, a phenethyl isothiocyanate marker, in dog plasma using solid-phase extraction and gas chromatography-mass spectrometry with chemical ionization.

Phenethyl isothiocyanate is unstable in aqueous media and at low pH, and rapidly degrades to phenethylamine. Concentrations of phenethylamine, a phenethyl isothiocyanate marker, in dog plasma, were determined utilizing solid-phase extraction and gas chromatography-mass spectrometry with chemical ionization using acetone as the reagent gas. Deuterated d5-amphetamine was used as an internal standard. After extraction, phenethylamine and d5-amphetamine were derivatized using MBHFBA. Ions monitored for d5-amphetamine were m/z 337 and 338; and for phenethylamine were m/z 318 and 319. Precision and accuracy were studied using control solutions prepared in naive dog plasma (80 and 300 ng/ml). Intra-day variability was determined using six replicates of each control solution analyzed on a single day. The relative standard deviation for the 80 ng/ml control was 12.9% and for the 300 ng/ml it was 12.1%. Relative accuracy was 10.9% for the low control and -4.1% for the high control. Inter-day variability was determined over a 6-day period. For the 80 and 300 ng/ml control solutions, the relative standard deviations were 15.8 and 9.1%, respectively, and relative accuracy values were 10.1 and -5.2%, respectively. Standard curves were prepared in naive dog plasma and were linear over the range of phenethylamine assayed (10-500 ng/ml). The results of this study indicate that the proposed method is simple, precise, accurate and sensitive enough for analysis of large numbers of plasma samples.

Animals

Second 46,XX male with MLS syndrome.

We report on a second 46,XX male with microphthalmia with linear skin defects (MLS) syndrome. In addition to microphthalmia and linear skin streaks, he had a secundum ASD, hypospadias with chordee, anal fistula, and agenesis of corpus callosum with colpocephaly. Biopsy of a linear streak showed smooth muscle hamartomata rather than the presumed dermal aplasia. Detailed ophthalmologic examination did not show retinal lacunae typical of Aicardi syndrome. DNA studies with distal Xp specific probes indicated a deletion in one X chromosome and fluorescence in situ hybridization (FISH) studies with X- and Y-specific probes demonstrated the presence of a derivative X chromosome from an X;Y translocation.

Agenesis of Corpus Callosum

Technical note: chromosomal and mtDNA analysis of Oliver.

Oliver is an African ape whose species identity has been debated in the popular media and by various scientists since the early 1970s. Although decisive morphological data has never been adduced on Oliver, many reports indicated that Oliver was morphologically unusual for a chimpanzee, particularly in his habitual bipedal posture. In addition, his diploid chromosome number was reported to be inconsistent with either human or chimpanzee, but instead intermediate between those species. We performed standard chromosomal studies which demonstrated that Oliver had the diploid number expected for a chimpanzee (2N = 48) and that the banding patterns of his chromosomes were typical for a chimpanzee and different from both humans and bonobos. We also sequenced a 312 bp region of his mitochondrial DNA D-loop region. Results indicated a high sequence homology to the Central African variety of chimpanzee, Pan troglodytes troglodytes. The highest percent homology was observed with a previously characterized specimen from Gabon, strongly suggesting that Oliver originated from this region.

Animals

Teratoma with trisomy 16 in a baboon (Papio hamadryas).

A teratoma was found during a planned cesarean section in a 10-year-old primigravida baboon. This teratoma had a female sex chromosome complement and trisomy for chromosome 16. This is the first report of a teratoma in a baboon and the first report of a chromosomal abnormality in a nonhuman primate teratoma. It is also the first case in a nonhuman primate to address the mechanism of origin. Through the use of genetic markers from human chromosomes 5, 8 and 17, the origin of the teratoma was shown to be most consistent with failure of meiosis II or endoreduplication in a mature ovum, while the trisomy for chromosome 16 originated after the formation of the tumor.

Animals

How does feature-based attention affect visual processing?

Five experiments are reported from which it is concluded that attending on the basis of a stimulus feature (e.g., red) does not directly affect the sensory quality of stimuli that possess that feature. Feature-based attention was manipulated in a visual search task by providing information about the probability that the target would possess a given feature (e.g., "The target has a 1.0 probability of being red when present.") Feature-based attention failed to aid performance under "data-limited" conditions (i.e., those under which performance was primarily affected by the quality of the stimulus) but did affect performance under conditions that were not data limited (Experiments 1-3). If attending to a feature had affected the sensory quality of stimuli, performance should have been aided under all conditions. Experiments 4 and 5 provided converging support for this conclusion.

Adolescent

Detection of doxepin and its major metabolite desmethyldoxepin in hair following drug therapy.

Doxepin is a tricyclic antidepressant that is widely prescribed for the treatment of mild depression. In this study, hair samples collected from a patient receiving 25 mg of doxepin daily were analyzed. Doxepin was administered to the patient for 4 months (June 15 to October 15, 1996). Five hair samples were collected: 1 and 3 months after doxepin therapy began and 1, 3, and 5 months after drug therapy ended. Solid-phase extraction was employed to isolate doxepin and its major metabolite desmethyldoxepin from the hair matrix, and gas chromatography-mass spectrometry (GC-MS) was used for quantitation of both drugs. Six-point standard curves (0.25-20 ng/mg) were prepared for both compounds with an internal standard (doxepin-d3). The standard curves for doxepin and desmethyldoxepin were linear over the range reported and had correlation coefficients of 0.984 and 0.985, respectively. The limit of quantitation for both analytes was 0.25 ng/mg of hair. In addition, the replicate analysis of control hair preparations was performed at two levels (2 ng/mg and 15 ng/mg) to determine intra- and interday variability. Doxepin and desmethyldoxepin were not detected in the patient's sample collected 1 month after doxepin therapy began. The samples collected 3 months after doxepin therapy began and 5 months after drug therapy was terminated had detectable amounts of doxepin and desmethyldoxepin. The highest concentrations of doxepin (mean, 0.59 ng/mg) and desmethyldoxepin (mean, 0.40 ng/mg) were found 5 months after doxepin therapy began, which was also 1 month after the patient had stopped using the drug. Five months after doxepin therapy was terminated, the drug and its metabolite were still present in the patient's hair. The concentration of doxepin in hair was always significantly higher than the concentration of desmethyldoxepin.

Adult

A baboon (Papio hamadryas) with an isochromosome for the long arm of the X.

A 5.5-yr-old female baboon was evaluated for sexual immaturity. She was small for her age and had normal external female genitalia. However, she lacked cyclical perineal turgescence and displayed atypical coloration of the perineal skin. Laparoscopy revealed a small uterus and absence of both ovaries. Cytogenetic analysis revealed a 42,X,i(X)(q10) karyotype. DNA analysis using loci DXS1683, which maps to Xp22.1, and DXS297, which maps to Xq27.3, was consistent with inheritance of the normal X chromosome from the dam and formation of the isochromosome Xq from the paternal X.

Animals

Baboon/human homologies examined by spectral karyotyping (SKY): a visual comparison.

Baboon (Papio hamadryas) metaphase chromosomes were analyzed using spectral karyotyping (SKY), a technique combining fluorescence microscopy, CCD-imaging, and Fourier spectroscopy. Results from a comparison of SKY analyses using probes derived from human chromosomes on baboon metaphases were consistent with the majority of comparative gene mapping data between the two species. These data were also compatible with earlier studies comparing macaque and human chromosomes. Human (HSA) chromosome 2 was homologous to baboon (PHA) chromosomes 12 (HSA 2q) and 13 (HSA 2p), whereas three baboon chromosomes corresponded to two different human chromosomes: PHA 3 to HSA 7 and HSA 21, PHA 7 to HSA 14 and HSA 15, and PHA 10 to HSA 20 and HSA 22. These results support the retained synteny between the Hominidae and Cercopithecidae genomes.

Animals

Glucocorticoid-resistant B-lymphoblast cell line derived from the Bolivian squirrel monkey (Saimiri boliviensis boliviensis).

The goal of the study reported here was to develop a continuous cell line from the squirrel monkey that expresses the species-specific phenotype of impaired sensitivity to glucocorticoids. Thirty milliliters of blood from a male Bolivian squirrel monkey (Saimiri boliviensis boliviensis) was fractionated, and the buffy coat was obtained and incubated in the presence of B95-8 cell-conditioned medium, an abundant source of Epstein-Barr virus (EBV), and 2 micrograms of cyclosporin A/ml. Cell growth was detected within 8 weeks, after which the cells were cloned by use of the limiting dilution method. One clone (4D8) was characterized in detail. The chromosomal count and G-banding pattern confirmed that the cells were of Bolivian squirrel monkey origin. The B-cell origin of these cells was indicated by electron microscopic analysis and was confirmed by expression of CD20. The cells stained strongly for LMP1, a marker of latent EBV infection, and occasionally for the lytic infection marker ZEBRA (BZLF1). The responsiveness of clone 4D8 cells to glucocorticoids was determined by comparing the effects of dexamethasone on cell growth and the induction of a glucocorticoid-inducible mRNA in 4D8 cells with the effects on a human EBV-transformed B-lymphoblast cell line (HL). Dexamethasone inhibited the growth of HL cells, with IC50 of approximately 9 nM, but had no effect on the growth of 4D8 cells. The induction of FK506-binding protein FKBP51 mRNA by dexamethasone was also significantly blunted in 4D8 cells. Thus, we have developed and characterized a squirrel monkey lymphoblastic cell line derived by transformation of B-lymphocytes with EBV; the cell line has diminished growth and transcriptional responses to glucocorticoids.

Animals

Studies in vivo of omega-gliadins in gluten sensitivity (coeliac sprue disease).

1. Highly purified omega-gliadins from wheat were used to challenge gluten-sensitized individuals. Characteristic responses by mucosal CD3(+) and gamma delta+ lymphocytes were demonstrated. Each lymphocyte subset showed an increase within 8-12 h post-challenge, indicating a specific response by the rectal mucosa to this gliadin species.2. Available sequence data for the omega-gliadins and homologous proteins from barley and rye indicate a common repeating octapeptide motif (consensus PQQPFPQQ). The results indicate, therefore, that the octapeptide repeat, or a contained sequence such as PQQP, plays an important role in the mucosal immunopathology of gluten sensitivity.

CD3 Complex

Basal ganglia choline levels in depression and response to fluoxetine treatment: an in vivo proton magnetic resonance spectroscopy study.

We have investigated proton magnetic resonance spectra of the basal ganglia in 41 medication-free outpatients with major depression, prior to starting an 8-week standardized trial of open-label fluoxetine, and 22 matched comparison subjects. Upon completing the trial, depressed subjects were classified as treatment responders (n = 18) or nonresponders (n = 23), based on changes in the Hamilton Depression Rating Scale. Depressed subjects had a lower area ratio of the choline resonance to the creatine resonance (Cho/Cr) than comparison subjects. This statistically significant difference between the depressed subjects and comparison subjects was more pronounced in the treatment responders than in the nonresponders. There were no differences in the relative volumes of gray matter or white matter in the voxel used for proton spectroscopy in depressed subjects relative to comparison subjects. These results are consistent with an alteration in the metabolism of cytosolic choline compounds in the basal ganglia of depressed subjects and, in particular, those who are responsive to fluoxetine.

Adult

Cochlear pathology induced by aminoglycoside ototoxicity during postnatal maturation in cats.

Cochlear pathology resulting from neonatal administration of the aminoglycoside antibiotic, neomycin sulfate, was studied in young kittens at 15-24 days postnatal. Hearing thresholds showed severe to profound hearing loss in all but one animal. Scanning electron microscopy demonstrated that initial hair cell degeneration occurred in the extreme base (hook region) of the cochlea and sequentially progressed to the basal, middle, then the apical coil of the cochlea. The first row of outer hair cells degenerated first, followed by row 2, then row 3; the last cells to degenerate in a given region were the inner hair cells. This pattern of hair cell degeneration is similar to that seen in adults with neomycin ototoxicity. In contrast, the spiral ganglion exhibited a different pattern of degeneration with initial cell loss occurring in the middle of the cochlea, about 40-60% from the base (approximately 2.8-8 kHz). Thus, neuronal degeneration apparently is not secondary to sensory cell loss, but rather comprises an independent process in these neonatal animals. Taken together, the findings suggest that the spiral ganglion cell loss in the middle cochlear turn results from increased aminoglycoside sensitivity associated with an earlier initial onset of function in these neurons as compared to other cochlear regions.

Animals

Care of asthma: allergy clinic versus emergency room.

BACKGROUND: Demographic and socioeconomic factors have an impact upon the morbidity and mortality rates of asthma in inner-city pediatric populations. Many pediatric patients with asthma use the emergency room as their primary care physician, while a smaller number of children with asthma use the allergy-immunology clinic. OBJECTIVE: We examined the demographic and socioeconomic characteristics of asthmatic patients using the emergency room as their primary care physician and of those attending the allergy-immunology clinic in the same inner-city hospital. We compared the morbidity and cost of care of asthmatic patients who received their medical care in the emergency room to that of those who received their care in the allergy-immunology clinic. METHODS: Fifty consecutive emergency room patients and 25 clinic patients were studied using an identical questionnaire. RESULTS: There was no difference between the two groups in the total number of individuals per household, children per family, monthly income, type or size of dwelling, financial problems purchasing medications, health insurance type, distance to the medical center, or education of the caretaker. Severity of asthma was not different in the two groups before the start of the study. The only significant demographic difference was in age: 10.6 years for the clinic group and 7.8 years for the emergency room group (P < .002). Clinically, in the year preceding the interview, the clinic group had significantly less nocturnal cough (P < .025), sleep interruption (P < .001), weekly asthma (P < .05), and emergency room visits (P < .09). The allergy clinic group had an approximate average savings of $137 per patient per year. Hospital admissions and emergency room costs were increased by a small group of three allergy clinic patients, decreasing the difference in the cost of care between the two groups. CONCLUSION: The data showed that patients who attended the emergency room and those who attended the allergy-immunology clinic were not demographically or socioeconomically different. The decreased morbidity of asthma and cost of care for the allergy clinic patients, as opposed to the emergency room patients, are likely due to the care given in the allergy-immunology clinic.

Allergy and Immunology

Perception without attention: evidence of grouping under conditions of inattention.

Many theories of visual perception assume that before attention is allocated within a scene, visual information is parsed according to the Gestalt principles of organization. This assumption has been challenged by experiments in which participants were unable to identify what Gestalt grouping patterns had occurred in the background of primary-task displays (A. Mack, B. Tang, R. Tuma, S. Kahn, & I. Rock, 1992). In the present study, participants reported which of 2 horizontal lines was longer. Dots in the background, if grouped, formed displays similar to the Ponzo illusion (Experiments 1 and 2) or the Müller-Lyer illusion (Experiment 3). Despite inaccurate reports of what the patterns were, participants' responses on the line-length discrimination task were clearly affected by the 2 illusions. These results suggest that Gestalt grouping does occur without attention but that the patterns thus formed may not be encoded in memory without attention.

Adolescent

Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study.

OBJECTIVE: The purpose of this study was to evaluate whether the concentration of beta-nucleoside triphosphate is lower in the basal ganglia of depressed subjects. METHOD: In vivo 31P magnetic resonance spectra were acquired from a 45-cm3 region surrounding the basal ganglia of 35 unmedicated depressed subjects and 18 comparison subjects. RESULTS: beta-Nucleoside triphosphate, which arises primarily from beta-ATP, was 16% lower in the depressed subjects than in the comparison subjects. CONCLUSIONS: The low level of beta-nucleoside triphosphate is consistent with an abnormality of high-energy phosphate metabolism in the basal ganglia of subjects with major depression.

Adenosine Triphosphate

The Clock Drawing Test for dementia of the Alzheimer's type: A comparison of three scoring methods in a memory disorders clinic.

OBJECTIVES: To examine the reliability and validity of the Clock Drawing Test when used as a cognitive screening instrument for mild to moderate dementia, and to compare different scoring mechanisms. DESIGN: Retrospective analysis of clock drawing performance using three published scoring methods (Shulman, Sunderland and Wolf-Klein). SETTING: Hospital-based memory disorders clinic. PARTICIPANTS: A sample of 28 consecutive patients attending the memory clinic for assessment who were given a diagnosis of Alzheimer's disease (mild or moderate) and 28 age- and sex-matched control subjects comprising 17 memory clinic attenders found to be normal and 11 community volunteers. MEASUREMENTS: Sensitivity and specificity of the three clock rating scales against memory clinic diagnoses of dementia using DSM-III-R; their respective interrater reliabilities; and comparisons of each with measures of cognitive impairment (the Mini-Mental State Examination and the Blessed Orientation-Information-Memory-Concentration Test), daily performance of basic and instrumental activities (the Blessed Dementia Scale) and depression (the Hamilton Rating Scale for Depression). RESULTS: All methods of scoring the Clock Drawing Test correlated well with measures of cognitive impairment (r = 0.57-0.73) and daily performance (r = 0.38-0.48), were independent of mild depression and demonstrated high sensitivity, specificity and interrater reliability. While all clock scales identified mild to moderate dementia reasonably well, the Shulman method performed best. In screening for dementia, clock drawing proved superior to the MMSE: 24/28 vs 20/28 cases identified. When compared with the MMSE, clock drawing provided additional diagnostic discrimination, identifying 7/8 AD patients with MMSE scores = 24. CONCLUSIONS: In a clinic population, clock drawing, especially if scored according to the Shulman scale and combined with the MMSE, is an extremely efficient test screening measure for mild to moderate dementia of the Alzheimer's type with low false negative and false positive rates. This may have implications for screening elderly populations.

Aged