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J C Miller

Publications and source records attributed to J C Miller.

At least 55 records · Page 3Linked to original sources
PubMed1995

Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection.

We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-alpha causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-alpha in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+ cell number > 400 cells per microliters, and 2 HIV-positive patients with CD4+ cell number < 400 cells per microliters), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+ cell number < 400 cells per microliters and 1 control subject. In 5 HIV subjects with abnormally low CD4+ cell counts ( < 400 cells per microliters), the number of days since seroconversion correlated significantly with low correlation between TNF-alpha and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-alpha and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.

Adult↗
PubMed1995

Mapping the mouse genome: current status and future prospects.

The mouse is the best model system for the study of mammalian genetics and physiology. Because of the feasibility and importance of studying genetic crosses, the mouse genetic map has received tremendous attention in recent years. It currently contains over 14,000 genetically mapped markers, including 700 mutant loci, 3500 genes, and 6500 simple sequence length polymorphisms (SSLPs). The mutant loci and genes allow insights and correlations concerning physiology and development. The SSLPs provide highly polymorphic anchor points that allow inheritance to be traced in any cross and provide a scaffold for assembling physical maps. Adequate physical mapping resources--notably large-insert yeast artificial chromosome (YAC) libraries--are available to support positional cloning projects based on the genetic map, but a comprehensive physical map is still a few years away. Large-scale sequencing efforts have not yet begun in mouse, but comparative sequence analysis between mouse and human is likely to provide tremendous information about gene structure and regulation.

Animals↗
PubMed1995

Mutant p53 is not fully dominant over endogenous wild type p53 in a colorectal adenoma cell line as demonstrated by induction of MDM2 protein and retention of a p53 dependent G1 arrest after gamma irradiation.

To determine whether a single mutational event in one p53 gene is sufficient to confer a significant growth advantage on a colonic epithelial cell, the 143(Ala) p53 mutation was previously expressed in the human colonic adenoma derived cell line AA/C1 (which is wild type for p53) and shown to have no effect on it's in vitro or in vivo growth characteristics. In this investigation, by expressing the 175(His), 248(Trp) or 273(His) mutations in the same AA/C1 cell line, we have shown that this failure to affect the growth of the cells was not mutant specific. We have also demonstrated, using induction of MDM2 protein and the ability of the cells to undergo a p53 dependent G1 arrest, that the 143(Ala), 175(His) or 248(Trp) transfected cells retain functional endogenous wild type p53 activity, and suggest that these p53 mutations would not have a fully dominant negative mode of action in vivo. In contrast, one of the two AA/C1 cell lines transfected with the 273(His) mutation did fail to cell cycle arrest after gamma irradiation, indicating that this mutation can act as a dominant negative. However even loss of wild type p53 function in this cell line was insufficient to directly effect the growth rate of the AA/C1 cells, suggesting that acquisition of the 273(His) mutation may contribute to malignant progression through genomic instability (by inhibiting the G1 arrest) and that other mutations are required before outgrowth of the cell population containing the p53 mutation.

Adenoma↗
PubMed1995

Gamma-radiation-induced apoptosis in human colorectal adenoma and carcinoma cell lines can occur in the absence of wild type p53.

The tumour suppressor gene p53 codes for a transcription factor which is thought to play a critical role in the induction of G1 cell cycle arrest and programmed cell death (apoptosis) following DNA damage by ionizing radiation. The aim of this investigation was to determine whether a p53 independent radiation-induced apoptosis pathway exists in human colon epithelial cell lines. This report describes the induction, by gamma-radiation, of apoptosis in the colorectal adenoma cell line S/RG/C2, and in the colorectal carcinoma cell line PC/JW, both of which lack wild type p53. In addition, flow cytometry revealed that both cell lines failed to arrest in G1 after radiation. Thus, although loss of wild type p53 may abrogate G1 arrest, radiation-induced apoptosis can still occur in human colonic tumour cell lines through a p53 independent mechanism.

Adenoma↗
PubMed1995

Chronic dietary lithium inhibits basal c-fos mRNA expression in rat brain.

1. Lithium is the most effective prophylactic agent used in the treatment of bipolar disorder. Although the acute effects of lithium include an inhibitory action on the phosphatidylinositol (PI) system, the longer term effects on signal transduction processes linked to this system are poorly understood. 2. An important consequence of activation of receptors linked to the PI pathway is activation of protein kinase C (PKC), which is involved in the induction of the proto-oncogene, c-fos. 3. The authors hypothesized that chronic lithium treatment, by inhibiting signaling through the PI/PKC pathway, might alter the expression of fos. 4. It was found that basal expression of c-fos was significantly reduced in cortical, hippocampal and hypothalamic brain areas of rats fed dietary lithium for 4 weeks. 5. The present results suggest that some of the effects of chronic lithium treatment may be mediated by alterations in signal transduction mechanisms linked to fos expression.

Animals↗
PubMed1995

Batch processing of 10,000 h of truck driver EEG data.

This paper describes the methods used to acquire and reduce a massive amount of EEG data (Wylie et al., 1990). The description is introduced by a review of a previous effort (Mackie and Miller, 1978). The earlier effort created much of the design philosophy for the second effort. The majority of data in the Paradox database came from 400 trips contributed by 80 commercial drivers driving both day and night revenue-cargo runs of 10 or 13 h each. The sleep and driving EEG data were collected with ambulatory Medilog recorders. Breathing and oxyhemoglobin measures were collected during sleep for sleep-apnea determinations. The sleep and driving-EEG data were placed in raw digitized files (128 samples/second), with the latter also available as compressed-band arrays for 20-s epochs, with associated Rechtschaffen and Kales (1968) manual scoring by polysomnographers for all EEG data. Sleep EEG, subjective driving performance and discrete-task data were also placed in the database, integrated and time-registered to within 1-s accuracy with the driving EEG data. Each truck was extensively instrumented for lateral lane position, steering wheel position, speed, video image of the roadway, and video image of the face. Each driver recorded body temperatures several times per day, provided Stanford Sleepiness Scale readings several times each day, and was connected to the Vagal Tone Monitor while driving. In addition, driving segments were prefaced and followed by the performance of the Critical Tracking Task, the Psychomotor Vigilance Task, and the Code Substitution Task. The database should serve as an international resource from which many investigators may draw data.

Accidents, Traffic↗
PubMed1995

Amylopectin starch promotes the development of insulin resistance in rats.

Starches that are high in amylopectin are digested and absorbed more quickly than starches with a high amylose content and produce larger postprandial glucose and insulin responses. The aim of this study was to test the hypothesis that feeding rats a diet containing quickly digested starch could promote insulin resistance. Sprague-Dawley rats were fed either a high amylopectin or high amylose diet (two 10-g meals per day), and insulin sensitivity was assessed after 9 wk by intravenous glucose tolerance test (IVGTT). In the rats fed the high amylopectin diet, glucose tolerance was significantly lower (P < 0.05) and the insulin response to IVGTT was twice as high as in rats fed the high amylose diet (P < 0.05). A second study using Wistar rats investigated the time course of these changes. Differences in the insulin response to the IVGTT were not evident at 4 wk but began to emerge at 8 wk, and by 12 wk the insulin response was 100% greater in rats fed the high amylopectin diet (P < 0.05) than in those fed the high amylose diet. In addition, basal plasma insulin concentration was higher in rats fed the high amylopectin diet (P < 0.05). There were no differences, however, in glucose tolerance at any time point. The results suggests that quickly digested starch promotes the development of insulin resistance in rats. The relatively slow time course resembles the normal development of insulin resistance in humans.

Amylopectin↗
PubMed1995

Early central nervous system response to HIV infection: sleep distortion and cognitive-motor decrements.

OBJECTIVE: To repeat and extend findings suggesting that sleep disturbance, excessive daytime sleepiness, and degraded cognitive-motor abilities may be early markers of central nervous system (CNS) involvement in HIV infection. DESIGN: A controlled, cross-sectional, prospective analysis. SETTING: Clinical research center at a teaching hospital and a military health research center. SUBJECTS: Twenty-three HIV-positive (mean CD4+ count, 387 +/- 162 x 10(6)/l) and 13 seronegative men who were Naval personnel or participants of the University of California, San Diego HIV Neurobehavioral Research Center. MAIN OUTCOME MEASURES: Nocturnal and daytime sleep electroencephalogram, electromyogram, and electrocardiogram. Simple and complex cognitive-motor performance assessed via computerized tasks. RESULTS: Comparison of sleep parameters based on HIV status, length of time infected, zidovudine use, and CD4+ count indicated that CD4+ T cells > 400 x 10(6)/l were associated with a distortion in nocturnal sleep characterized by increased stages 3 and 4 non-rapid eye movement (i.e., slow-wave) sleep in the latter portion of the night and reduced nocturnal awakenings. HIV-positive patients were no sleepier in the daytime than controls. Cognitive-motor performance revealed deficits in both accuracy and efficiency for HIV-positive patients. CONCLUSION: Asymptomatic HIV-positive patients with CD4+ counts > 400 x 10(6)/l demonstrate a statistically significant increase in slow-wave sleep during the latter portion of the night and less arousability. CD4+ lymphocyte count in the early phases of HIV infection appears to differentiate between various levels of HIV disease progression with respect to certain CNS measurements of nocturnal sleep and cognitive-motor performance. Sleep structure distortion remains one of the earliest and most consistently replicable physiological signs of HIV infection. This distortion may provide a link to immune function, disease progression, and cognitive-motor disability in HIV infection.

AIDS Dementia Complex↗
PubMed1995

A satiety index of common foods.

OBJECTIVE: The aim of this study was to produce a validated satiety index of common foods. DESIGN AND SUBJECTS: Isoenergetic 1000 kJ (240 kcal) servings of 38 foods separated into six food categories (fruits, bakery products, snack foods, carbohydrate-rich foods, protein-rich foods, breakfast cereals) were fed to groups of 11-13 subjects. Satiety ratings were obtained every 15 min over 120 min after which subjects were free to eat ad libitum from a standard range of foods and drinks. A satiety index (SI) score was calculated by dividing the area under the satiety response curve (AUC) for the test food by the group mean satiety AUC for white bread and multiplying by 100. Thus, white bread had an SI score of 100% and the SI scores of the other foods were expressed as a percentage of white bread. RESULTS: There were significant differences in satiety both within and between the six food categories. The highest SI score was produced by boiled potatoes (323 +/- 51%) which was seven-fold higher than the lowest SI score of the croissant (47 +/- 17%). Most foods (76%) had an SI score greater than or equal to white bread. The amount of energy eaten immediately after 120 min correlated negatively with the mean satiety AUC responses (r = -0.37, P < 0.05, n = 43) thereby supporting the subjective satiety ratings. SI scores correlated positively with the serving weight of the foods (r = 0.66, P < 0.001, n = 38) and negatively with palatability ratings (r = -0.64, P < 0.001, n = 38). Protein, fibre, and water contents of the test foods correlated positively with SI scores (r = 0.37, P < 0.05, n = 38; r = 0.46, P < 0.01; and r = 0.64, P < 0.001; respectively) whereas fat content was negatively associated (r = -0.43, P < 0.01). CONCLUSION: The results show that isoenergetic servings of different foods differ greatly in their satiating capacities. This is relevant to the treatment and prevention of overweight and obesity.

Adult↗
PubMed1994

Cytoskeletal alterations in cultured cardiomyocytes following exposure to the lipid peroxidation product, 4-hydroxynonenal.

Damage to the cardiac myocyte sarcolemma following any of several pathological insults such as ischemia (anoxia) alone or followed by reperfusion (reoxygenation), is most apparent as progressive sarcolemmal blebbing, an event attributed by many investigators to a disruption in the underlying cytoskeletal scaffolding. Scanning electron microscopic observation of tissue cultured rat neonatal cardiomyocytes indicates that exposure of these cells to the toxic aldehyde 4-hydroxynonenal (4-HNE), a free radical-induced, lipid peroxidation product, results in the appearance of sarcolemmal blebs, whose ultimate rupture leads to cell death. Indirect immunofluorescent localization of a number of cytoskeletal components following exposure to 4-HNE reveals damage to several, but not all, key cytoskeletal elements, most notably microtubules, vinculin-containing costameres, and intermediate filaments. The exact mechanism underlying the selective disruption of these proteins cannot be ascertained at this time. Colocalization of actin indicated that whereas elements of the cytoskeleton were disrupted by increasing length of exposure to 4-HNE, neither the striated appearance of the myofibrils nor the lateral register of neighboring myofibrils was altered. Monitoring systolic and diastolic levels of intracellular calcium ([Ca2+]i) indicated that increases in [Ca2+]i occurred after considerable cytoskeletal changes had already taken place, suggesting that damage to the cytoskeleton, at least in early phases of exposure to 4-HNE, does not involve Ca(2+)-dependent proteases. However, 4-HNE-induced cytoskeletal alterations coincide with the appearance of, and therefore suggest linkage to, sarcolemmal blebs in cardiac myocytes. Although free radicals produced by reperfusion or reoxygenation of ischemic tissue have been implicated in cellular damage, these studies represent the first evidence linking cardiomyocyte sarcolemmal damage to cytoskeletal disruption produced by a free radical product.

Aldehydes↗
PubMed1994

The carnivore connection: dietary carbohydrate in the evolution of NIDDM.

We postulate a critical role for the quantity and quality of dietary carbohydrate in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Our primate ancestors ate a high-carbohydrate diet and the brain and reproductive tissues evolved a specific requirement for glucose as a source of fuel. But the Ice Ages which dominated the last two million years of human evolution brought a low-carbohydrate, high-protein diet. Certain metabolic adaptations were therefore necessary to accommodate the low glucose intake. Studies in both humans and experimental animals indicate that the adaptive (phenotypic) response to low-carbohydrate intake is insulin resistance. This provides the clue that insulin resistance is the mechanism for coping with a shortage of dietary glucose. We propose that the low-carbohydrate carnivorous diet would have disadvantaged reproduction in insulin-sensitive individuals and positively selected for individuals with insulin resistance. Natural selection would therefore result in a high proportion of people with genetically-determined insulin resistance. Other factors, such as geographic isolation, have contributed to further increases in the prevalence of the genotype in some population groups. Europeans may have a low incidence of diabetes because they were among the first to adopt agriculture and their diet has been high in carbohydrate for 10,000 years. The selection pressure for insulin resistance (i.e., a low-carbohydrate diet) was therefore relaxed much sooner in Caucasians than in other populations. Hence the prevalence of genes producing insulin resistance should be lower in the European population and any other group exposed to high-carbohydrate intake for a sufficiently long period of time.

Agriculture↗
PubMed1994

A genetic map of the mouse with 4,006 simple sequence length polymorphisms.

We have constructed a genetic map of the mouse genome containing 4,006 simple sequence length polymorphisms (SSLPs). The map provides an average spacing of 0.35 centiMorgans (cM) between markers, corresponding to about 750 kb. Approximately 90% of the genome lies within 1.1 cM of a marker and 99% lies within 2.2 cM. The markers have an average polymorphism rate of 50% in crosses between laboratory strains. The markers are distributed in a relatively uniform fashion across the genome, although some deviations from randomness can be detected. In particular, there is a significant underrepresentation of markers on the X chromosome. This map represents the two-thirds point toward our goal of developing a mouse genetic map containing 6,000 SSLPs.

Animals↗
PubMed1994

Importance of glycemic index in diabetes.

To date there are 11 medium to long-term studies that have specifically used the glycemic index (GI) approach to determine the clinical gains in diabetes or lipid management. All but one study produced positive findings. On average, low-GI diets reduced glycosylated hemoglobin by 9%, fructosamine by 8%, urinary C-peptide by 20%, and day-long blood glucose by 16%. Cholesterol was reduced by an average of 6% and triglycerides by 9%. These are modest improvements but so too were the changes to the diet. Unlike high-fiber diets, low-GI diets are "user friendly." As part of studies on the GI of foods, we determined the glycemic and insulin responses to 44 foods containing simple sugars. Their mean (+/- SE) GI was 62 +/- 14, which compares favorably with bread (GI = 73, glucose = 100). There was often no difference in the GI between the sweetened and unsweetened product. The time has come to reassess the value of GI in planning meals for diabetics.

Blood Glucose↗
PubMed1994

Replacing starch with sucrose in a high glycaemic index breakfast cereal lowers glycaemic and insulin responses.

OBJECTIVE: To test the hypothesis that replacing starch with sugar in a processed breakfast cereal that has a high glycaemic index could significantly decrease glycaemic and insulin responses. DESIGN: Subjects consumed in random order three equi-carbohydrate meals based on a popular puffed rice cereal containing three levels of sucrose (0, 21 and 43 g). Postprandial glucose and insulin responses were compared using the incremental area under the curve (AUC). SUBJECTS: Twelve healthy volunteers (5 males and 7 females) with normal glucose tolerance drawn from the university community, mean age 23 years (range: 20 to 27 year), mean body mass index 22.6 kg/m2 (range: 18.6 to 31.2 kg/m2). RESULTS: Glycaemia was significantly lower after the meal containing the highest amount of sugar (glucose AUC 101.7 +/- 14.0 mmol/l.120 min) compared with the non-sweetened cereal (155.5 +/- 18.0 mmol/l.120 min, P < 0.01). There was a significant inverse correlation between the amount of sucrose incorporated and the degree of glycaemia (analysis of covariance coefficient = -1.25, P = 0.00). Similarly, the plasma insulin response was significantly lower after the highest sugar meal (insulin AUC 2267 +/- 346 microU/ml.120 min) compared with the meal without sugar (3505 +/- 365 microU/ml.120 min, P < 0.01). CONCLUSIONS: We found a significant reduction in glycaemic and insulin responses when sugar replaced the rapidly digested starch in a processed breakfast cereal, i.e. the opposite of what is commonly believed. Thus sweetened breakfast cereals may not compromise glycaemic control more so than the unsweetened counterpart.

Adult↗
PubMed1993

A genetic linkage map of the mouse: current applications and future prospects.

Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.

Animals↗