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PubMed1998

Chromosomal basis of X chromosome inactivation: identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation.

A number of genes have been identified that escape mammalian X chromosome inactivation and are expressed from both active and inactive X chromosomes. The basis for escape from inactivation is unknown and, a priori, could be a result of local factors that act in a gene-specific manner or of chromosomal control elements that act regionally. Models invoking the latter predict that such genes should be clustered in specific domains on the X chromosome, rather than distributed at random along the length of the X. To distinguish between these possibilities, we have constructed a transcription map composed of at least 23 distinct expressed sequences in an approximately 5.5-megabase region on the human X chromosome spanning Xp11.21-p11.22. The inactivation status of these transcribed sequences has been determined in a somatic cell hybrid system and correlated with the position of the genes on the physical map. Although the majority of transcribed sequences in this region are subject to X inactivation, eight expressed sequences (representing at least six different genes) escape inactivation, and all are localized to within a region of less than 370 kb. Genes located both distal and proximal to this cluster are subject to inactivation, thereby defining a unique multigene domain on the proximal short arm that is transcriptionally active on the inactive X chromosome.

Animals↗
PubMed2001

Combustion modeling and performance evaluation in a full-scale rotary kiln incinerator.

This work summarizes the results of numerical investigations and in situ measurements for turbulent combustion in a full-scale rotary kiln incinerator (RKI). The three-dimensional (3D) governing equations for mass, momentum, energy, and species, together with the kappa - epsilon turbulence model, are formulated and solved using a finite volume method. Volatile gases from solid waste were simulated by gaseous CH4 distributed nonuniformly along the kiln bed. The combustion process was considered to be a two-step stoichiometric reaction for primary air mixed with CH4 gas in the combustion chamber. The mixing-controlled eddy-dissipation model (EDM) was employed to predict the conversion rates of CH4, O2, CO2, and CO. The results of the prediction show that reverse flows occur near the entrance of the first combustion chamber (FCC) and the turning point at the entrance to the second combustion chamber (SCC). Temperature and species are nonuniform and are vertically stratified. Meanwhile, additional mixing in the SCC enhances postflame oxidation. A combustion efficiency of up to 99.96% can be achieved at approximately 150% excess air and 20-30% secondary air. Reasonable agreement is achieved between numerical predictions and in situ measurements.

Air Pollution↗
PubMed1996

Selection for longevity favors stringent metabolic control in Drosophila melanogaster.

Models of the evolution of life span predict, and gerontological studies show, a relation between nutrient use and life span. This study examines the role and comparative use of nutrients in long- and short-lived populations of D. melanogaster selectively bred for age-at-reproduction, without respect to metabolism or feeding rate. We test the hypotheses that selection for life span has favored the restriction of nutrient use and that the observed effect of low population density during development is a consequence of modifying nutrient use. The use of nutrients was measured here by the uptake of radiolabeled glucose, its incorporation into lipid and protein, and by the in vivo metabolic flux through the pentose shunt. Measurements show that uptake, incorporation, and flux are severely limited in long-lived stocks, compared to short-lived populations of the same stage and stage of development. Raising long-lived stocks at low population numbers relieves the restriction on metabolism in larvae, increasing incorporation and flux, and causes adult life span to decline. Larvae of long-lived populations appear to feed less actively, suggesting that the reduction in use of nutrients could simply be from reduced intake. Changes in total soluble protein correspond with measurements of uptake, incorporation, and flux. Soluble protein is substantially less in long-lived stocks, before pupation, but catches up in early adulthood to that in the short-lived populations. Despite different nutrient use by larval populations, only slight differences are found in development rate. They are insufficient to account for the differences observed in longevity.

Age Factors↗
PubMed2003

Food stamp program participation is positively related to obesity in low income women.

This study examined the relationship between Food Stamp Program (FSP) participation and the obesity of low income individuals using data from the National Longitudinal Survey of Youth 1979. Obesity was defined as body mass index >or= 30 kg/m(2). The data were arranged as a panel with multiple observations per individual, and the models of obesity included current and long-term FSP participation, additional demographic, socioeconomic and environment characteristics and individual fixed effects. Individual fixed effects were used to take into account unobserved differences across individuals that did not vary over time. In ordinary least squares models, current and long-term FSP participation were significantly related to the obesity of low income women (P < 0.05), but not of low income men. For low income women, current participation in the FSP was associated with a 9.1% increase in the predicted probability of current obesity. Participation in the FSP in each of the previous five years compared to no participation over that time period was associated with approximately a 20.5% increase in the predicted probability of current obesity. These models did not control for food insecurity, and this omission potentially complicates the interpretation of the FSP participation variables.

Adolescent↗
PubMed2003

The relations of effortful control and reactive control to children's externalizing problems: a longitudinal assessment.

In this study, we examined the role of negative emotionality as a moderator of the relations of effortful control and overcontrol (versus undercontrol) with children's externalizing problem behaviors; we also examined the longitudinal relations among these variables. Teachers' and parents' reports of children's negative emotionality, effortful control, overcontrol and externalizing problem behaviors were obtained at T1 (N=199; M age=89.51 months) and again 2 (T2) and 4 years (T3) later. In addition, children's effortful control was assessed with an observed measure of persistence. In a T3 concurrent structural equation model, effortful control, but not overcontrol, was negatively related to children's T3 externalizing problem behaviors. In regression analyses, the negative relation between T3 effortful control and externalizing problem behaviors was strongest at high levels of T3 negative emotionality. In the best-fitting longitudinal structural equation model, both T1 effortful control and T1 overcontrol negatively predicted externalizing problems at T1, whereas T3 effortful control (but not T3 overcontrol) was significantly negatively related to T3 externalizing problem behaviors when controlling for T1 externalizing problem behaviors.

Affect↗
PubMed1972

On the regulation of depth and rate of breathing.

1. The relationships between the depth of a breath and the durations of the inspiratory and expiratory phases have been studied in cat and in man during rebreathing, and in cat using artificial inflations of different magnitudes and timings.2. In the cat, the apparent volume threshold for termination of inspiration (Hering-Breuer threshold) decreased with time from the onset of the inspiratory phase.3. Both in rebreathing experiments and with artificially imposed inflations in the cat, the inspiratory duration T(I) was dependent upon tidal volume V(T), and this dependence could be expressed by a hyperbolic relationship of the form (V(T)-V(0)) T(I) = C where V(0) and C are constants.4. The time course of this ;Hering-Breuer' threshold was dependent on intact vagus nerves. After vagotomy the inspiratory duration remained essentially constant with changes in tidal volume produced either by artificial inflation or by the increased respiratory drive due to accumulation of CO(2) during rebreathing.5. In man during rebreathing, the relation between volume and inspiratory duration typically showed two different characteristics. 1, at tidal volumes up to 1.5-2 times eupnoeic values, inspiratory duration did not change as tidal volume increased in response to increased P(CO2). This range of operation has been designated range 1. 2, as tidal volume increased above this range 1 a second range designated range 2 was observed where inspiratory duration was volume dependent in the same manner as in the cat.6. In cat under pentobarbitone anaesthesia, a range 1 operation was not seen except after vagotomy. However, under urethane anaesthesia a range 1 plus a range 2 operation could be seen.7. The differences between cat and man appeared to be largely quantitative rather than qualitative.8. In both cat and man, expiratory duration was dependent on inspiratory duration, usually with a linear relationship.9. The experimental results were assembled in the form of an inspiratory characteristic and a timing relationship that serve as a model of the respiratory mechanisms controlling the depth and rate of breathing. The model predicts that the depth and duration of a breath are related in a definite manner fixed by the system characteristics and that ventilation is adjusted by setting the appropriate operating point on these characteristics. The operating point is determined primarily by how quickly lung volume increases, i.e. the rate of increase of inspiratory motor activity.

Adult↗
PubMed1984

Homeostatic capability of rate-sensitive feedback system: mathematical model.

We have predicted the mathematical model of rate-sensitive feedback control system and have investigated its homeostatic capability by using computer simulations. The results are summarized as follows. By installing a cyclic enzyme system as feedback control element, we could assume the rate-sensitive feedback system at molecular level. This type of feedback had realistic constant-value control capability for external perturbations. This feedback system was more effective for the exclusion of perturbation than was the concentration-sensitive feedback. A large-loop feedback was more stable for perturbation than was short-loop feedback. In sequential feedback system, every key enzyme sensitive to feedback control had to vary the activity at same time for the system to keep homeostasis.

Animals↗
PubMed1983

Dynamic response of local pulmonary blood flow to alveolar gas tensions: analysis.

It has been reported that left lower lobe pulmonary blood flow (Q) and alveolar CO2 decrease then oscillate in a progressively damped manner when the lobar inspirate is changed from pure O2 to N2. This damped oscillatory response of lobar Q is abolished by maintaining lobar CO2 constant. We set out to develop the simplest mathematical model that can simulate these experimental results by using techniques derived from control theory. Different models were tested. The simplest model that predicts the experimental data incorporates an exponential decrease of lobar Q to local alveolar hypoxia (time constant 3 min) and a damped oscillatory response of lobar Q to local alveolar hypocapnia. The response to hypocapnia has two components: a vasodilator effect possibly related to intracellular [H+] and a vasoconstrictor effect possibly related to changes of molar CO2. Both these components (time constants of 4.8 min) interact with each other by cross-coupled elements (time constants of 4.8 min). This model can be used to forecast results so that its validity can be tested by experiment.

Animals↗
PubMed2003

Importance of cutaneous feedback in maintaining a secure grip during manipulation of hand-held objects.

Previous research has shown that grip and load forces are modulated simultaneously during manipulation of a hand-held object. This close temporal coupling suggested that both forces are controlled by an internal model within the CNS that predicts the changes in tangential force on the fingers. The objective of the present study was to examine how the internal model would compensate for the loss of cutaneous sensation through local anesthesia of the index and thumb. Ten healthy adult subjects (5 men and 5 women aged 20-57 yr) were asked to grasp, lift, and hold stationary, a 250 g object for 20 s. Next, the subjects were asked to perform vertical oscillatory movements over a distance of 20 cm at a rate of 1.0 Hz for 30 s. Eleven trials were performed with intact sensation, and 11 trials after a local ring-block anesthesia of the index and thumb with bupivacain (5 mg/ml). During static holding, loss of cutaneous sensation produced a significant increase in the safety margin. However, the grip force declined significantly over the 20-s static hold period. During oscillatory arm movements, grip and load forces were continuously modulated together in a predictive manner as suggested by Flanagan and Wing. Again, the grip force declined over the 30-s movement, and 7/10 subjects dropped the object at least once. With intact sensation, the object was never dropped; but with the fingers anesthetized, it was dropped on 36% of the trials, and a significant slip occurred on a further 12%. The mean correlation between the grip and load forces for all subjects deteriorated from 0.71 with intact sensation to 0.48 after digital anesthesia. However, a cross-correlation calculated between the grip and load forces indicated that the phase lag was approximately zero both with and without digital anesthesia. Taken together, the data from the present study suggest that cutaneous afferents are required for setting and maintaining the background level of the grip force in addition to their phasic slip-detection function and their role in adapting the grip force/load force ratio to the friction on initial contact with an object. Finally, at a more theoretical level, they correct and maintain an internal model of the physical properties of hand-held objects.

Adult↗
PubMed1997

Relation of operator volume and experience to procedural outcome of percutaneous coronary revascularization at hospitals with high interventional volumes.

BACKGROUND: Although an inverse relation between physician caseload and complications has been conclusively demonstrated for several surgical procedures, such data are lacking for percutaneous coronary intervention, and the ACC/AHA guidelines requiring > or = 75 cases per year for operator "competency" are considered by some physicians to be arbitrary. METHODS AND RESULTS: From quality-controlled databases at five high-volume centers, models predictive of death and the composite outcome of death, Q-wave infarction, or emergency bypass surgery were developed from 12,985 consecutively treated patients during 1993 through 1994. Models had moderate to high discriminative capacity (area under ROC curves, 0.65 to 0.85), were well calibrated, and were not overfitted by standard tests. These models were used for risk adjustment, and the relations between both yearly caseload and years of interventional experience and the two adverse outcome measures were explored for all 38 physicians with > or = 30 cases per year. The average physician performed a mean +/- SD of 163 +/- 24 cases per year and had been practicing angioplasty for 8 +/- 5 years. Risk-adjusted measures of both death and the composite adverse outcome were inversely related to the number of cases each operator performed annually but bore no relation to total years of experience. Both adverse outcomes were more closely related to the logarithm of caseload (for death, r = .37, P = .01; for death, Q-wave infarction, or bypass surgery, r = .58, P < .001) than to linear caseload. CONCLUSIONS: In this analysis, high-volume operators had a lower incidence of major complications than did lower-volume operators, but the difference was not consistent for all operators. If these data are validated, their implications for hospital, physician, and payer policy will require exploration.

Angioplasty, Balloon, Coronary↗
PubMed1999

Predictors of plasma concentrations of DDE and PCBs in a group of U.S. women.

We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs) in a group of 240 women, controls from a breast cancer case-control study nested in the Nurses' Health Study. We considered personal attributes such as age, serum cholesterol, region of residence, adiposity, lactation, and dietary intake. DDE levels increased 0.17 ppb/year of age (p = 0.0003), and PCBs increased 0.08 ppb (p = 0.0001). DDE and PCBs increased 0.20 (p = 0.02) and 0.13 ppb (p = 0.001), respectively, per 10 mg/dl serum cholesterol. Women living in the western United States had higher levels of DDE (mean = 11.0 ppb; p = 0.003), and women in the Northeast and Midwest had higher levels of PCBs (mean = 5.6 ppb; p = 0.0002) as compared to women from other parts of the country (mean DDE = 6.3; mean PCBs = 4. 5 ppb). Levels of DDE could not be predicted from consumption of meat, fish, poultry, dairy products, vegetables, fruits, and grains. There was a positive association between fish consumption and PCB concentrations among women in the Northeast and Midwest. Using data from the cases in the nested case-control study to assess the predictive ability of the models, we confirmed that the most reliable predictors of DDE were age and serum cholesterol, and the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast. The null results for the majority of the food variables suggest that specific dietary factors, other than fish, are not currently a substantial contributor to human exposure to DDE and PCBs.

Adult↗
PubMed2004

An in vitro study of the ultrasonic axial transmission technique at the radius: 1-MHz velocity measurements are sensitive to both mineralization and intracortical porosity.

UNLABELLED: The ultrasonic axial transmission technique allows for investigating skeletal sites such as the cortical layer of long bones (radius, tibia, phalanges). Using synchrotron radiation microCT, we investigated, in vitro, the relationships between 1-MHz axial transmission SOS measurements at the radius and site-matched measurements of C.Th, POR, MIN, and vBMD. INTRODUCTION: The ultrasonic axial transmission technique allows for investigating skeletal sites such as the cortical layer of long bones (radius, tibia, phalanges). MATERIALS AND METHODS: Using synchrotron radiation microCT, we investigated, in vitro, the relationships between 1-MHz axial transmission speed of sound (SOS) measurements at the radius and site-matched measurements of cortical thickness (C.Th), intracortical porosity (POR), tissue mineralization (MIN), and volumetric BMD (vBMD). SOS measurements were based on bidirectional axial transmission and were performed with a 1-MHz proprietary probe on 39 excised human radii. RESULTS: The highest correlations between SOS values and bone parameters (R(2)(SOS/POR) = 0.28, p < 10(-3); R(2)(SOS/MIN) = 0.38, p < 10(-4); R(2)(SOS/vBMD) = 0.57, p < 10(-3)) were found for bone parameters assessed in a 1-mm-thick periosteal region of the cortex rather than throughout the whole cortex. The observed moderate correlation between SOS and C.Th values (R(2)(SOS/C.Th) = 0.20, p < 10(-2)) disappeared when controlled for other variables. The two best multilinear predictive models, including either BMD alone or the pair of dependent variables MIN and POR (all assessed in the periosteal cortex), were equally accurate in predicting SOS values (R(2)(SOS/(POR,MIN)) = 0.59, p < 10(-5); R(2)(SOS/vBMD) = 0.57, p < 10(-5)). CONCLUSION: For the first time, the respective adjusted contributions of POR (-24 m/s%(-1)) and tissue mineralization (+3.5 m/s/mg/cm(-3)) to SOS values were assessed. These results suggest potential sensitivity of axial transmission SOS values to changes in cortical bone status under different pathological conditions or treatments affecting POR and/or tissue mineralization.

Aged↗
PubMed2006

Surgery for patients with severe supratentorial intracerebral hemorrhage.

INTRODUCTION: Little information is available on the efficacy of aggressive treatment such as surgery in improving the outcome of severely affected patients after supratentorial intracerebral hemorrhage (ICH). Our objective was to assess the effect of hematoma removal and ventricular drainage on the mortality of patients with severe primary supratentorial ICH. METHODS: We studied 103 consecutive patients who were admitted to the intensive care unit and diagnosed with primary supratentorial ICH. The impacts of clinical factors on 30-day mortality were assessed, including surgery, Glasgow Coma Scale (GCS) score and pupillary abnormality at admission, hematoma volume, and other related factors. RESULTS: The 30-day mortality rate was 42%, and the median time between admission and death was 3 days (range: 1 to 27 days). Hematoma removal and ventricular drainage, within the first 24 hours of admission, were performed on 11 and 17 patients, respectively. Two patients who were treated with removal and four with drainage died. A logistic regression model for predicting 30-day mortality was performed. After controlling for GCS score, pupillary abnormality, hydrocephalus, and hematoma volume, hematoma removal was identified as an independent predictor of survival (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.02 to 0.92). Ventricular drainage also tended to decrease mortality rate greatly (OR, 0.31; 95% CI, 0.06 to 1.76). Patients with GCS scores of 3 or 4 were 4.01 times more likely to die (95% CI, 1.13 to 14.26) than those with GCS of at least 5. CONCLUSIONS: Hematoma removal may reduce the mortality rate of patients with severe supratentorial ICH.

Adult↗
PubMed2005

Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease.

Dopamine replacement therapy effectively treats the early motor symptoms of Parkinson's disease (PD). However, its association with the development of motor complications limits its usefulness in late stages of the disease. Adenosine A(2A) receptors are localised to the indirect striatal output function and control motor behaviour. They are active in predictive experimental models of PD and appear to be promising as the first major non-dopaminergic therapy for PD. Istradefylline is a novel adenosine A(2A) receptor antagonist currently in Phase III clinical trials for efficacy in patients with PD; results from Phase II clinical trials demonstrated that it provides a clinically meaningful reduction in 'off' time and an increased 'on' time with non-troublesome dyskinesia in levodopa-treated patients with established motor complications, and is safe and well tolerated.

Adenosine A2 Receptor Antagonists↗
PubMed2004

On the relation between sensory input and action.

The role of sensory return in movement has recently been considered in relation to models involving feedforward control and in the comparison of predicted and actual states. The author suggests that sensory feedback may also have other effects at the level of movement initiation. The experiences of 3 individuals with differing impairments are reported, 1 with acute withdrawal of movement and position sense, 1 with acute meningitis, and the 3rd after prolonged immobilization following a heel injury. All were surprised to find difficulty in turning an intention to move into action in the affected body areas. One suggested that he had "forgotten what to do," even though the original injury had healed. The path from intention to movement may be dependent on feedback from the peripheral sensory apparatus at levels below attention, at least until voluntary action is required.

Biofeedback, Psychology↗
PubMed1999

Ethnic differences in the behavior of hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to examine the clinical presentation, prognostic factors, and survival rates of patients with hepatocellular carcinoma (HCC) and to examine differences between Asian and non-Asian patients with HCC. METHODS: A review of the clinical characteristics and laboratory evaluations for 76 patients in two different broad ethnic groups (Asians [Group 1] and non-Asians [Group 2]) who underwent treatment for HCC from 1977-1995 was performed. Chi-square and Cox regression analyses were performed to assess factor interaction and association with survival. RESULTS: A total of 24 patients in Group 1 and 52 patients in Group 2 were reviewed. Of the clinical variables examined, a higher rate of a history of hepatitis B positivity was observed in Group 1 compared with Group 2 (32% vs. 6%; P=0.001). Among the 76 patients with HCC, a 1-year survival estimate of 41.4% was found. There was a borderline significant difference in survival between Group 1 and Group 2 with a 1-year survival estimate of 29.5% versus 46.9%, respectively (P=0.08). Better overall survival was found in patients who had tumors that were resectable (P=0.0001), had an alpha-fetoprotein level <10 ng/mL (P=0.02), or were a younger age at the time of diagnosis (P=0.01). There was a trend for Asian race (P=0.08) to be associated with poorer survival. When these risk factors were entered into a multivariate analysis, tumor resectability and non-Asian race were most predictive of improved survival (model P value = 0.007). When controlling for the multiple variables most often reported to be associated with HCC, Asians had a significantly lower survival than non-Asians (P<0.01). CONCLUSIONS: In this study it appears that the outcome for Asian patients with hepatoma is worse than for non-Asian patients, even when controlling for factors commonly associated with HCC. Biologic or social factors that are not appreciated currently may be involved in Asian patients with HCC, contributing to a poorer clinical outcome.

Adolescent↗
PubMed2001

Angiogenesis: a therapeutic target in arthritis.

A variety of pharmacological strategies are being subjected to clinical trial to inhibit neovascularization of solid tumors. Increased angiogenesis is also a key component of synovitis and bone modeling in arthritis. Molecular mechanisms and pathological consequences of blood vessel growth in arthritis are now being elucidated. Preclinical studies of angiogenesis inhibitors in animal models of inflammatory arthritis support the hypothesis that inhibition of neovascularization may reduce inflammation and joint damage. Clinical data are consistent with these models being predictive of efficacy in rheumatoid arthritis. However, controlled studies of specific anti-angiogenic agents in human arthritis remain limited. Further studies are required to demonstrate that pharmacological agents can effectively inhibit articular angiogenesis, and ameliorate inflammation and subsequent joint damage. Potential toxicity of angiogenesis inhibitors in reproduction, growth and development and wound repair may be circumvented by short-term or local application, or by targeting molecular mechanisms that are specific to pathological rather than physiological angiogenesis.

Angiogenesis Inhibitors↗