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Biomedical subjects

R L Phillips

Publications and source records attributed to R L Phillips.

At least 73 records · Page 4Linked to original sources
PubMed1996

Activation of memory circuits during cue-elicited cocaine craving.

Evidence accumulated over more than 45 years has indicated that environmental stimuli can induce craving for drugs of abuse in individuals who have addictive disorders. However, the brain mechanisms that subserve such craving have not been elucidated. Here a positron emission tomographic study shows increased glucose metabolism in cortical and limbic regions implicated in several forms of memory when human volunteers who abuse cocaine are exposed to drug-related stimuli. Correlations of metabolic increases in the dorsolateral prefrontal cortex, medial temporal lobe (amygdala), and cerebellum with self-reports of craving suggest that a distributed neural network, which integrates emotional and cognitive aspects of memory, links environmental cues with cocaine craving.

Adult↗
PubMed1996

Experiences with a distributed virtual patient record system.

TeleMed is a distributed diagnosis and analysis system, which permits physicians who are not collocated to consult on the status of a patient. The patient's record is dynamically constructed from data that may reside at several sites but which can be quickly assembled for viewing by pointing to the patient's name. Then, a graphical patient record appears, through which consulting physicians can retrieve textual and radiographic data with a single mouse click. TeleMed uses modern distributed object technology and emerging telecollaboration tools.

Computer Communication Networks↗
PubMed1996

Peptide T and glucose metabolism in AIDS dementia complex.

AIDS dementia complex (ADC) is the most common presenting neurologic manifestation of human immunodeficiency virus (HIV)-1 infection. We report FDG-PET studies in a 39-year-old man who had ADC and completed a 12-wk treatment protocol with 1.2 mg/day of intranasal peptide T, one before and one after 12 wk of treatment with peptide T. Peptide T is an octapeptide under investigation for treatment of ADC patients. Values of rCMRglc were converted to Z scores using the mean and standard deviation of values of rCMRglc in three HIV-seronegative matched controls, each of which was studied twice, at the beginning and end of a 12-wk interval. Thirty-five of 60 regions assayed showed Z scores with absolute values > or = 3 (considered abnormal) in the baseline study. Regions with high absolute values of Z scores were located in subcortical areas and in the limbic system, and to a lesser degree in the frontal, temporal and parietal lobes. Thirty-four of these 35 regions showed remission (decrease in the absolute values of Z scores) after treatment. Only one region showed no improvement in the second study. Three regions with absolute values of Z scores < 3 in the baseline study manifested Z scores with magnitudes > or = 3 in the second study. These preliminary observations suggest that functional neuroimaging techniques provide a useful tool in the evaluation of the response to treatment in ADC patients.

AIDS Dementia Complex↗
PubMed1995

Dynamics of maize endosperm development and DNA endoreduplication.

Endosperm development in Zea mays is characterized by a period of intense mitotic activity followed by a period in which mitosis is essentially eliminated and the cell cycle becomes one of alternating S and G phases, leading to endoreduplication of the nuclear DNA. The endosperm represents a significant contribution to the grain yield of maize; thus, methods that facilitate the study of cellular kinetics may be useful in discerning cellular and molecular components of grain yield. Two mathematical models have been developed to describe the kinetics of endosperm growth. The first describes the kinetics of mitosis during endosperm development; the second describes the kinetics of DNA endoreduplication during endosperm development. The mitotic model is a modification of standard growth curves. The endoreduplication model is composed of six differential equations that represent the progression of nuclei from one DNA content to another during the endoreduplication process. Total nuclei number per endosperm and the number of 3C, 6C, 12C, 24C, 48C, and 96C nuclei per endosperm (C is the haploid DNA content per nucleus) for inbred W64A from 8 to 18 days after pollination were determined by flow cytometry. The results indicate that the change in number of nuclei expressed as a function of the number of days after pollination is the same from one yearly crop to another. These data were used in the model to determine the endosperm growth rate, the maximum nuclei number per endosperm, and transition rates from one C value to the next higher C value. The kinetics of endosperm development are reasonably well represented by the models. Thus, the models provide a means to quantify the complex pattern of endosperm development.

Cell Nucleus↗
PubMed1995

Genetic factors influencing murine hematopoietic productivity in culture.

In order to study a previously described genetic difference manifested in stem cell kinetics of specific mouse strains, effects of this putative gene, stk, were measured on growth and expansion of stem and progenitor cell populations ex vivo. Bone marrow cells from each of two inbred mouse strains, C57BL/6J and DBA/2J, were placed into separate bioreactor cultures perfused continuously with growth medium containing erythropoietin (Epo), interleukin-3 (IL-3), granulocyte-macrphage colony stimulating factor (GM-CSF), and Kit ligand as well as 5% CO2. Expansion of cell numbers reached 20-fold for DBA/2J and 10-fold for C57BL/6J marrow within about 1 week of culture. Significant production was also seen of colony-forming unit (CFU)-GM (up nine-fold from input levels) just prior to the cell production peak, and, importantly, moderate expansion of day 12 colony-forming unit-spleen (CFU-S; two- to threefold) occurred as well, although CFU-S production peaked at a relatively short 4 days. CFU-S and CFU-GM levels declined rapidly in culture, either because of unfavorable growth conditions or terminal differentiation. Attempts to remove toxic metabolites by increasing the media perfusion rate resulted in a boost in cell expansion capability by DBA/2J marrow. In bioreactors in which stromal cells were established before marrow inoculation, there was greater expansion of CFU-S (especially by DBA/2J) and CFU-GM, although total cell yield appeared to be unaffected, perhaps because the maximum cell density had already been reached. The relative high potential for CFU-S expansion measured in DBA/2J marrow over that of C57BL/6J will be useful in following genetic contributions to bone marrow production capacity.

Animals↗
PubMed1995

Cerebral glucose utilization in polysubstance abuse.

Regional cerebral glucose metabolism in subjects with histories of polysubstance abuse was compared to that in control subjects who were drawn from the same community. The substance abuse group showed lower absolute metabolic rates for glucose in lateral occipital gyrus and higher normalized metabolic rates in temporal and frontal areas, including orbitofrontal cortex. It is suggested that some patterns of brain function associated with polysubstance abuse may represent consequences of drug exposure, or they could reflect pre-existing differences that may be relevant to the etiology and maintenance of polysubstance abuse.

Adult↗
PubMed1995

Magnetic resonance imaging reveals no ventriculomegaly in polydrug abusers.

Previous studies of cerebral structure in substance abusers yielded controversial results, largely due to issues of subject selection and/or limitations of experimental techniques. The purpose of the present study was to assess whether the ventricle-to-brain ratio (VBR), determined volumetrically by magnetic resonance imaging (MRI), differed in polysubstance abusers (n = 10), as compared with age-matched controls (n = 10). Subjects were male volunteers 21-39 years of age. The values of VBR in the polydrug abuse group were not larger than those in control group, nor was there any tendency toward relative ventriculomegaly in the substance abusers. Therefore, the present findings provide no evidence that polysubstance abuse produces abnormalities of gross brain structure in relatively young and physically healthy men.

Adult↗
PubMed1995

An improved method to calculate cerebral metabolic rates of glucose using PET.

UNLABELLED: PET methods for single-scan measurement of the cerebral metabolic rate of glucose (CMRglc) generally involve sampling of radioactivity in arterial plasma over the course of the experiment. The purpose of this study was to develop an analytic procedure that would require substantially fewer plasma samples to measure CMRglc using the single-scan method. METHODS: This technique uses a model for the curve describing the time course of radioactivity in plasma. RESULTS: This model obviates the need to draw arterial samples at short time intervals or at all during the first 30 min after radiotracer injection. The new technique uses six samples to provide the same accuracy and precision as the conventional method provides with 30 or more samples. CONCLUSION: The proposed method greatly simplifies quantitative PET studies of glucose metabolism.

Adult↗
PubMed1994

Genetic instability of plant tissue cultures: breakdown of normal controls.

Plants regenerated from relatively undifferentiated callus cultures possess a vast array of genetic changes. Such variations can result in useful agricultural and horticultural products. For other purposes, however, variations in traits other than those of interest may be undesirable--for example, using cultured cells for genetic engineering. Any steps made toward understanding the basis of tissue culture-induced genetic variation should be helpful in developing a more stable and manipulatable somatic cell system. This review provides a glimpse at the specific kinds of genetic changes encountered among regenerated plants and their progeny. Included among these variations are cytosine methylation alterations of the genome. The repeat-induced point mutation (RIP) phenomenon, reported for filamentous fungi, is invoked to provide a framework to consider the origin of variation in plant tissue cultures.

5-Methylcytosine↗
PubMed1994

Buprenorphine reduces cerebral glucose metabolism in polydrug abusers.

Buprenorphine is a mixed opioid agonist-antagonist, which acts as a partial mu agonist and a kappa antagonist. The present study evaluated the acute effects of buprenorphine on cerebral glucose metabolism (CMRglc) in six human substance abusers using a double-blind, placebo-controlled, counterbalanced, crossover design. Each subject participated in two positron emission tomographic (PET) studies, 1 week apart, following the injection of buprenorphine (1 mg, intramuscularly) and placebo. Buprenorphine significantly reduced CMRglc and the regional cerebral metabolic rate for glucose (rCMRglc) by up to 32% in all but three of 22 bilateral and in 4 midline regions (p < .05). No region showed an increase in rCMRglc. Buprenorphine also produced miosis, respiratory depression, and subjective ratings of euphoria and sedation in comparison to placebo (p < .05). These observations extend previous findings of reduced CMRglc following acute treatment with morphine and other nonopioid euphorigenic drugs.

Adult↗
PubMed1994

Morphine effects on the spontaneous electroencephalogram in polydrug abusers: correlations with subjective self-reports.

The spontaneous electroencephalogram (EEG) was recorded after the intramuscular (IM) injection of morphine sulfate (15, 30 mg) or saline (0.9% NaCl). Correlations between changes in EEG spectral power and subjective self-reports, as measured on subscales of the Addiction Research Center Inventory (ARCI), were evaluated. Morphine increased alpha 1 and alpha 2 power and theta power, and attenuated the increase in delta power observed after placebo. Positive correlations were found between the change in alpha 1, alpha 2, beta 1, and beta 2 power in response to 30 mg of morphine and scores on Morphine-Benzedrine Group (MBG) subscale of the ARCI. Negative relationships were observed between changes in alpha 1, and beta 2 and scores on the Pentobarbital Chlorpromazine Alcohol Group (PCAG) subscale. The findings indicate that positive subjective effects of opioids, as measured by the MBG subscale, are related to increases in alpha and beta activity and are associated with reduction of opioid-induced sedation, as measured by the PCAG subscale.

Adult↗
PubMed1994

Cocaine-induced increases in EEG alpha and beta activity: evidence for reduced cortical processing.

To understand the effects of cocaine on the cerebral cortex, 14 male polydrug abusers were enrolled in a study on the effects of cocaine on the electroencephalogram (EEG). The experimental treatments were placebo, 20 mg cocaine or 40 mg cocaine i.v. administered in a double-blind, pseudorandom design. The EEG was recorded from 13 electrode positions over the left hemisphere during a 3-minute baseline recording and for 30 minutes after initiation of the i.v. injection. The spectral power for delta, theta, alpha and beta EEG bands was calculated from data collected in each 3-minute interval. Cocaine significantly increased beta in frontal and central areas and enhanced alpha in frontal and temporal regions. Cocaine-induced increases in EEG beta power had a cortical distribution similar to those produced by barbiturates and benzodiazepines. As all of these drugs reduce cortical glucose metabolism, the increases in beta power may reflect a reduction in cortical neural activity.

Adult↗
PubMed1994

Cancer incidence among California Seventh-Day Adventists, 1976-1982.

Cancer incidence was monitored in a population of 34,000 Seventh-day Adventists in California. By religious belief, Adventists do not consume tobacco, alcohol, or pork and approximately one-half adhere to a lacto-ovovegetarian lifestyle. Only a small percentage are pure vegetarians. Comparisons of cancer-incidence rates in this population with an external reference population were completed by calculating standardized morbidity ratios (SMRs) for all cancer sites. Also, within the population, relative risks were calculated by using data obtained from a detailed lifestyle questionnaire that members of the study population completed. For all cancer sites combined in males, the SMR was lower in the Adventists (SMR = 0.73). The SMR was also lower in males for most individual cancer sites. However, prostate cancer risk was higher. For females, the all-cancer SMR was lower but not significantly so (SMR = 92). Most site-specific SMRs were lower, although not as much as the male SMRs. The SMR for endometrial cancer was significantly higher in female Adventists.

Adult↗
PubMed1993

Tissue culture-induced DNA methylation variation in maize.

Twenty-one progeny lines derived from tissue cultures of two embryo sources of maize inbred strain A188 were examined for DNA methylation changes. Total DNA was cut with the isoschizomers Hpa II and Msp I and probed with 18 single-copy Pst I genomic clones and two cDNA clones. Eight of these probes could detect both increases and decreases in methylation. With these probes 39% of the families were found to contain an altered methylation pattern. All changes represented a decrease in methylation. The other 12 probes could detect only increases in methylation; no methylation variation was seen with these probes. Fifteen percent of the methylation changes were homozygous in the original regenerated plant. Changes were stably inherited upon two generations of self-pollination. No sequence variation was observed in Msp I-digested DNA from the same 21 progeny lines. Certain probes detected methylation changes much more often than others. Our study provides evidence that demethylation occurs at a high frequency and could be an important cause of tissue culture-induced variation. Occurrence of the frequent homozygous alterations in original regenerated plants implies a non-random mutational mechanism.

Base Sequence↗
PubMed1993

Apoptosis and hematopoiesis in murine fetal liver.

The fetal mouse liver (FL) is an organ of intense, but transient, hematopoietic activity during mid-gestation, with erythropoiesis being predominant during days 11 through 16. It therefore seemed reasonable to expect that hematopoietic cytokines, such as erythropoietin (epo), interleukin-3 (IL-3), and stem cell factor (SCF), may play important roles in maintaining a homeostatic balance of erythropoiesis and apoptosis in liver during ontogeny. First, we determined the effects of these growth factors on hematopoiesis by measuring colony formation and hemoglobin synthesis of cultured FLs. Secondly, we determined the protection from apoptosis afforded by these cytokines, using electrophoretic analysis of DNA and by flow cytometry of FL cells deprived in culture of epo, IL-3, and SCF. Erythropoietin was necessary and alone sufficient for hemoglobin synthesis in colony-forming units-erythroid colonies, but IL-3 was a required cofactor to obtain maximal development of burst-forming units-erythroid colonies. SCF alone caused little colony formation in methylcellulose cultures of FLs, but when combined with epo and IL-3, it had dramatic effects both on the number of colonies and their size. Secondly, indices of apoptosis were determined by measuring DNA fragmentation caused by endogenous nuclease activity in apoptotic cells. Liver cells from cultures without cytokines showed the extensive degradation of DNA to low molecular weight nucleosomal oligomers, which is characteristic of apoptosis. Protection from apoptosis afforded by epo directly corresponded to the level of erythropoiesis in FLs of different gestational age. Erythropoietin was by far the most critical cytokine in sparing FL cells from apoptosis. Analyses of agarose gels showed that SCF and IL-3 alone had no apparent effect in reducing the amount of DNA in fragments, and when combined with epo they had no more protective effect than that provided by epo alone. However, using the more sensitive flow cytometric determination of cells with subdiploid amounts of DNA, SCF, and IL-3 alone had measurable protective effects that were less than those caused by epo. Thus, we show that normal, untransformed cells of the developing hematopoietic system not only require cytokines for proliferation and differentiation, but they have an initial and absolute requirement of them for protection from apoptosis.

Animals↗
PubMed1993

Plant genetics: out with the old, in with the new?

Plant breeding represents an evolving technology based largely on genetic principles. Approximately one-half of the increased yields of major crop plants can be attributed to the genetic improvement of the crop. Although the breeding technology and undergirding science are sound, additional information on the biochemical pathways underlying agronomic and quality traits and their genetic control would allow new genetic technologies to be used more fully. Current developments in molecular biology, plant cell and tissue culture, genetic engineering, and use of molecular genetics will facilitate the selection of complex traits. Genetic improvement of plants in the future will be based on an integration of modern plant-breeding methods and the new genetic technologies. Thus, the new genetic approaches do not represent a replacement technology but will add to the arsenal of tools available for improving crops.

Agriculture↗