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PubMed1979

Transient CO2 elimination and storage as functions of the ventilatory response to CO2.

The effect on CO2 storage and elimination of variations in the slope and intercept of the ventilatory response to CO2 curve was examined. Theoretical and experimental results show that although CO2 elimination rate following a transient ventilatory disturbance is decreased at low ventilatory response slopes, this decrease can be compensated by elevated PCO2 intercepts, or thresholds. Conversely, high CO2 elimination rate following a ventilatory disturbance due to a high ventilatory response slope can be off-set by a depressed PCO2 threshold. The results suggest that elevated thresholds which often accompany depressed ventilatory response slopes may be part of a compensatory mechanism for minimizing transient hypercapnia and acidosis.

Animals↗
PubMed1982

Effect of temperature on the ventilatory response curve to carbon dioxide in anaesthetized cats.

Effects of body temperature on the ventilatory control system were studied in 17 anaesthetized cats. At different body temperatures (stabilized within 0.1 degrees C) CO2 response curves were measured in each cat. In with chloralose-urethan anaesthetized cats it was found that in the body temperature range of 34-40 degrees C, in which neither shivering nor panting occurred, no statistically significant trend with temperature was found in the slope (S) and the extrapolated intercept on the PaCO2-axis (B) of the linear CO2 response curve during hyperoxia as well as hypoxia. In two with pentobarbital anaesthetized cats similar results were obtained. The resting ventilation (at FICO2 = 0) did not change significantly, while the resting PaCO2 during hyperoxia showed a trend to increase with temperature just reaching the level of significance (P less than 0.05). Breathing frequency increased significantly with temperature (P less than 0.0005). When body temperature was elevated above 41 degrees C both the slope (S) and the intercept of the CO2 response curve (B) decreased. In three cats ventriculo-cisternal perfusion was performed and no apparent influence of body temperature was found on the relation between the PCSFCO2 and PETCO2 and on the VE-PCSFCO2 response curves. These findings show that body temperature has no important modifying effect on the ventilatory response to CO2 in anaesthetized cats in the temperature range of 34-40 degrees C.

Anesthesia, General↗
PubMed1986

Comparison of five methods of analyzing respiratory pressure-volume curves.

Five methods of analyzing the deflation limb of respiratory pressure-volume (PV) curves obtained from seven groups of rats that had undergone various treatments were compared. The five methods utilized measurements of: y intercept and slope with simple exponential curve fitting; area under the curve; volumes at fixed pressures; shape constant, k, of the sigmoid curve described by Paiva et al. (Respir. Physiol. 23:317, 1975); and quasi-static compliance. The seven groups of rats were treated as follows: control (n = 10); high tar/nicotine cigarette smoke exposure (n = 10); low tar/nicotine cigarette smoke exposure (n = 9); intratracheal elastase (n = 10); intratracheal elastase plus sham smoke exposure (n = 10); intratracheal elastase plus high tar/nicotine cigarette smoke exposure (n = 9); and intratracheal elastase plus low tar/nicotine cigarette smoke exposure (n = 10). Elastase treatment caused a leftward and upward shift of the PV curve and this shift was augmented by exposure to either high tar/nicotine or low tar/nicotine cigarette smoke. Using Duncan's multiple range test, we found that the y-intercept measurement of method 1, the area under the curve, volumes at fixed pressures, and quasi-static compliance methods were better able to differentiate PV curves between groups than were the slope measurement of method 1 and the shape constant measurement of method 4.

Animals↗
PubMed1989

Accommodation and presbyopia in the human eye--aging of the anterior segment.

Ocular biometric parameters and accommodative amplitude were measured by various techniques in 100 normal emmetropic human subjects age 18-70 yr. Anterior chamber depth decreased and lens thickness increased linearly over the entire age group. Accommodative amplitude declined linearly until a stable nadir was reached at about age 50 yr. The respective slopes and intercepts of the age-dependent decline in anterior chamber depth were essentially the same for measurements made independently by optical pachmetry, A-scan ultrasonography, and slit-lamp Scheimpflug photography. The age-dependent increase in lens thickness differed in slope and intercept for measurements made by photography and ultrasonography if the generally accepted lenticular sound velocity was assumed for all subjects. However, if putative lenticular sound velocity was adjusted for age, the relationships given by the two techniques were essentially identical. Total anterior segment length (defined as the distance between the anterior corneal and posterior lens surfaces), vitreous cavity length (distance between the posterior lens and anterior retinal surfaces), and total globe length were all independent of age. This constellation of findings indicates that the human lens grows throughout adult life while the globe does not, that thickening of the lens completely accounts for shallowing of the anterior chamber with age, but that the posterior surface of the lens remains fixed in position relative to the cornea and retina.

Accommodation, Ocular↗
PubMed1991

Longitudinal Gompertzian analysis of breast cancer mortality in the U.S., 1962-1987: demonstration of a disorder displaying complex deterministic mortality dynamics.

Age-adjusted mortality rates for breast cancer (BC) in the United States from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-adjusted BC mortality rate distributions for women display two distinct Gompertzian slopes. Between age 15 and 40 years, age-adjusted BC mortality rate distributions intercepted at age 33.5 years and mortality rate (per 100,000) 5.83. Between age 50 and 85 years, age-adjusted BC mortality rate distributions intercepted at age 60.4 years and mortality rate 77.0. These two distinct Gompertzian regions correspond to the clinical and biological classification of BC into pre- and post-menopausal varieties. The observation that postmenopausal BC increases in environments conducive to survival and that premenopausal BC increases in environments that are less favorable becomes understandable when BC mortality dynamics are viewed from a competitive and deterministic perspective.

Adolescent↗
PubMed1982

A thromboxane synthetase inhibitor reorients endoperoxide metabolism in whole blood towards prostacyclin and prostaglandin E2.

During incubation of citrated blood at 37 degrees C the levels of 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and prostaglandin E2 (PGE2) remain constant, but rise markedly within one minute after the addition of collagen, particularly when thromboxane synthetase is blocked. The amount of 6-keto PGF1 alpha formed is dose-dependent for both collagen and the thromboxane synthetase inhibitor (UK-37,248). Moreover, the number of platelets will determine the extent of the 6-keto PGF1 alpha jump, that does not occur when blood is drawn after aspirin ingestion. The production of 6-keto PGF1 alpha in function of time is composed of a fast platelet-related (intercept) and a slower probably leukocyte-dependent contribution (slope). In the absence of UK-37,248 the intercept is 115 +/- 85 pg/ml, the slope is 12.9 +/- 7.7 pg/min/ml whereas in the presence of the thromboxane synthetase inhibitor they are 411 +/- 177 pg/ml and 56.2 +/- 25 pg/min/ml respectively. The present findings indicate that a thromboxane synthetase inhibitor, by not only reducing thromboxane A2 production but also enhancing prostacyclin generation with blood is exposed to thrombogenic stimuli such as collagen, should be superior to aspirin as an antithrombotic agent, although possible interference by enhanced PGE2 production should be taken into account.

Blood Platelets↗
PubMed1993

Induction of hyperhydration in rats by IP loading with graded concentrations of NaCl solution.

IP loads of NaCl solution (1% of body weight) varying in concentration from 0.15-1.0 M were used to assess their ability to induce hyperhydration in rats that were allowed access to water for 6 h after loading. The hypertonic concentrations (0.25, 0.50, and 1.0 M) increased water intake in a concentration-related fashion. Only loads of 0.50 and 1.0 M NaCl solution increased urine output above that of water-loaded controls. All hypertonic concentrations increased fluid exchange (i.e., water intake less urine output) significantly. There was a direct concentration-related increase in accumulative mean fluid exchange (delta FE, fluid exchange of NaCl-loaded group less that of control group). There was also a direct concentration-related increase in the time of hyperhydration. When related to each other, delta FE was a direct linear function of time of hyperhydration. The slope and intercept of this relationship were compared with those found in an earlier study for angiotensin II (AngII) and isoproterenol (ISO), both potent dipsogens. Comparison revealed that slopes, but not intercepts, of the relationship between delta FE and time of hyperhydration for any two of the three treatments differed significantly. These data suggest that a given time of hyperhydration can be achieved at a lower delta FE with NaCl loads than with administration of either AngII or ISO. This suggests, in turn, that loading with NaCl solutions produces a more effective hyperhydration than is achieved with administration of either AngII or ISO.

Angiotensin II↗
PubMed1988

Comparison between brain paste and polymer [125I]standards for quantitative receptor autoradiography.

[125I]standards prepared from grey and white matter from rat brain have been compared to commercially available polymer-based standards using two types of radiation-sensitive film for use in quantitative receptor autoradiography. There was a linear relationship between the natural log of optical density and radioactivity (dpm/mm2) for both types of tissue standard exposed to Hyperfilm [3H] or betamax from 1-14 days. No difference between either the slopes or intercepts of these lines for each period of exposure was identified. There was also no significant difference between the slopes and intercepts of tissue-based standards and the lowest 5 activity levels of polymer standards. Over the complete range of ten radioactivity levels of polymer standards, the linear relationship was lost and a quadratic function was the best model for describing the relationship between 1n optical density and radioactivity. Moreover, a linear relationship between section thickness over the range frequently used in receptor studies (5-20 microns) was observed. These results suggest that the lower activity levels of polymer standards are comparable to tissue standards and can be used for quantitative receptor autoradiography.

Animals↗
PubMed1996

Revalidation of the in vitro alkaline elution/rat hepatocyte assay for DNA damage: improved criteria for assessment of cytotoxicity and genotoxicity and results for 81 compounds.

The in vitro alkaline elution/rat hepatocyte assay is a sensitive assay for genotoxicity, measured as DNA strand breaks induced in primary cultures of rat hepatocytes after 3-h treatments with test compounds. Since DNA degradation can be rapid and extensive in dead and/or dying cells, the original criteria for a positive result in the assay were that a compound induce a 3.0-fold or greater increase in the elution slope (for the terminal phase of alkaline elution from 3 to 9 h) in the absence of significant cytotoxicity (defined as relative cell viability of less than 70% by trypan blue dye exclusion; TBDE). Recently we have shown that false-positive results can still be obtained due to cytotoxicity when loss of membrane integrity is a late event in toxic cell death relative to the induction of endonucleolytic DNA degradation. To improve the ability of the assay to discriminate between genotoxic vs. cytotoxic effects of chemicals, we have evaluated additional assays of cytotoxicity including cell adenosine triphosphate (ATP) and potassium (K+) content, tetrazolium dye reduction (MTT), TBDE after a further 3-h recovery incubation without test chemicals (delayed toxicity), cell blebbing and endonucleolytic DNA degradation (double-strand breaks; DSBs) assessed by pulsed-field gel electrophoresis (PFGE). We have also evaluated 2 parameters derived from the elution data which can indicate extensive, cytotoxicity-induced DNA degradation: the fraction of the DNA recovered in the neutral lysis/rinse fraction and the gamma-intercept of the extrapolation of the 3-9-h segment of the elution curve. Twenty-eight rodent non-carcinogens that are negative (or inconclusive) in the Ames assay with no, or limited, other evidence of genotoxicity, and 33 genotoxins, most of which are also carcinogens, were evaluated. The results showed that DNA degradation as measured by a 1-h PACE (Programmed Autonomously Controlled Electrodes)/PFGE assay was a sensitive indicator of cytotoxicity which correlated well with results of the other cytotoxicity indicators. The delayed TBDE (after a 3-h recovery), intracellular potassium and ATP assays as well as the gamma-intercept parameter were also shown to be sensitive and in some cases complementary measures of cytotoxicity. Using new criteria based on these data of an induced slope (treatment slope-negative control slope) of 0.020 for the 3- to 9-h elution period and cytotoxicity limits of 70% relative viability for the delayed TBDE assay and 50% for intracellular ATP content, the assay scores the genotoxicity of these 61 reference compounds with an overall accuracy of 92%. Test results using these new criteria are provided for an additional 20 compounds (5 non-genotoxic carcinogens and 15 compounds whose genotoxic and carcinogenic potential are unknown or equivocal).

Adenosine Triphosphate↗
PubMed1986

Fibroblasts from patients with inherited predisposition to retinoblastoma exhibit normal sensitivity to the mutagenic effects of ionizing radiation.

Retinoblastoma (RB) is a cancer of the retina which characteristically occurs in early childhood. Bilateral RB is an inherited form of this disease. Such patients are at greatly increased risk of subsequently developing second tumors in mesenchymal tissue, especially in areas exposed to ionizing radiation therapy. Fibroblasts from bilateral RB patients have been reported to be more sensitive than normal fibroblasts to the cytotoxic effects of ionizing radiation. Because xeroderma pigmentosum patients have a hereditary predisposition to UV-induced cancer and the cells of such patients are abnormally sensitive to the cytotoxic and mutagenic effects of UV radiation, we compared fibroblasts from 6 bilateral RB patients and 3 normal individuals for their sensitivity to the mutagenic effects of cobalt 60, using resistance to 6-thioguanine (TG) as the genetic marker. The results showed no statistically significant difference between the two types of cell lines. The slope of the weighted least squares line representing the frequency of TG-resistant cells induced in the RB populations as a function of dose was 17 +/- 6 (S.E.)/10(6) cells/Gy with an intercept of 0.09 Gy; that for the normal cells was 17 +/- 7/10(6) cells/Gy with an intercept of 0.14 Gy. We also compared 8 bilateral RB cell lines and 9 age-matched normal cell lines for their sensitivity to the cytotoxic effect of 60Co, using survival of colony-forming ability. The cloning efficiency of the unirradiated RB cell lines ranged from 22% to 76% with an average of 52%; that of the normal cell lines from 21% to 89% with an average of 64%. The results showed the RB cells were somewhat more sensitive than the normal cells. The mean D0 for the RB cell lines ranged from 0.99 +/- 0.01 (S.E.) to 1.69 +/- 0.04 Gy with a weighted average of 1.44 +/- 0.08 Gy; that of the normal cell lines ranged from 1.42 +/- 0.17 to 2.24 +/- 0.10 Gy, with a weighted average of 1.79 +/- 0.11 Gy. The difference in means was estimated to be 0.34 +/- 0.14. The mean for the RB cell lines is statistically significantly lower than the mean for the normal cell lines, at a significance level ca. 1%.

Adolescent↗
PubMed1982

A simple exercise test in borderline and sustained essential hypertension.

We measured blood pressure and heart rate at rest and during exercise on a bicycle ergometer in 19 patients with borderline hypertension, in 58 with sustained essential hypertension and in a group of 30 healthy subjects of the same age. On each subject, we determined the systolic blood pressure/heart rate curve during exercise and calculated the slope and intercept. In patients with borderline hypertension, blood pressure was elevated in basal conditions but was within the normal range at the end of exercise. This caused an increased intercept (P less than 0.001) and a reduced slope (P less than 0.05) of the curve. In patients with sustained hypertension, blood pressure was elevated throughout the exercise test. This caused an increased slope (P less than 0.001) of the blood pressure/heart rate curve. The slope of the curve correlated negatively with basal heart rate in borderline hypertensive patients (P less than 0.01) and correlated positively with basal total peripheral resistance in sustained hypertensive patients (P less than 0.01). Exercise testing can help one diagnose borderline and sustained hypertension and predict the evolution of borderline hypertension toward fixed hypertension.

Adult↗
PubMed1994

CO2 crop growth enhancement and toxicity in wheat and rice.

The effects of elevated CO2 on plant growth are reviewed and the implications for crop yields in regenerative systems are discussed. There is considerable theoretical and experimental evidence indicating that the beneficial effects of CO2 are saturated at about 0.12% CO2 in air. However, CO2 can easily rise above 1% of the total gas in a closed system, and we have thus studied continuous exposure to CO2 levels as high as 2%. Elevating CO2 from 340 to 1200 micromoles mol-1 can increase the seed yield of wheat and rice by 30 to 40%; unfortunately, further CO2 elevation to 2500 micromoles mol-1 (0.25%) has consistently reduced yield by 25% compared to plants grown at 1200 micromoles mol-1; fortunately, there was only an additional 10% decrease in yield as the CO2 level was further elevated to 2% (20,000 micromoles mol-1). Yield increases in both rice and wheat were primarily the result of increased number of heads per m2, with minor effects on seed number per head and seed size. Yield increases were greatest in the highest photosynthetic photon flux. We used photosynthetic gas exchange to analyze CO2 effects on radiation interception, canopy quantum yield, and canopy carbon use efficiency. We were surprised to find that radiation interception during early growth was not improved by elevated CO2. As expected, CO2 increased quantum yield, but there was also a small increase in carbon use efficiency. Super-optimal CO2 levels did not reduce vegetative growth, but decreased seed set and thus yield. The reduced seed set is not visually apparent until final yield is measured. The physiological mechanism underlying CO2 toxicity is not yet known, but elevated CO2 levels (0.1 to 1% CO2) increase ethylene synthesis in some plants and ethylene is a potent inhibitor of seed set in wheat.

Biomass↗
PubMed1982

Hemispheric asymmetry, early visual processes, and serial memory comparison.

Observers indicated whether a single probe letter presented to the left visual field/right hemisphere (LVF-RH) or to the right visual field/left hemisphere (RVF-LH) matched one of two, three, four, or five set letters in both name and case. For positive trials during the initial experimental session, the slope of the linear memory set size reaction time function was increased by perceptually degrading the probe letter on LVF-RH trials, but not on RVF-LH trials. In addition, perceptual degradation of the probe letter increased the intercept of the memory set size function more on RVF-LH trials than on LVF-RH trials. During subsequent experimental sessions, the same pattern of intercept results was obtained but perceptual degradation of the probe no longer changed the slope for either LVF-RH or RVF-LH trials. However, the slopes were uniformly lower on RVF-LH trials than on LVF-RH trials. The major results are consistent with hypothesized right-hemisphere efficiency for early processing stages and left-hemisphere efficiency for serial processing of alphanumeric information. The results further illustrate the importance of separating stages of processing in studies of cerebral laterality and indicate that the relative difficulty of the various stages can be a determinant of laterality results.

Cerebral Cortex↗
PubMed1991

Studies on the mechanism of bile salt-independent bile flow impairment in streptozotocin-induced hepatotoxicity.

The main factors involved in the impairment of formation of the bile salt-independent bile flow (BSIF) in streptozotocin (SZ)-treated rats were examined. Twenty-four hours after SZ injection (50 mg/kg body wt, i.v.) bile flow, bile salt output and biliary excretion of the major inorganic electrolytes (sodium, chloride and bicarbonate) were significantly diminished. The relationship between bile flow and bile salt output obtained during the administration of sodium taurocholate at stepwise-increasing rates indicated that bile salt-independent bile flow (y-intercept) was diminished by 37% in SZ-treated rats. The relationship between electrolyte output and bile salt output showed that the fractions of sodium, chloride and bicarbonate excreted independently of bile salt (y-intercept) decreased to 59%, 47% and 67% of the control values respectively, while the amount of electrolyte secreted per unit of bile salt secreted was unaffected in SZ-treated rats. The hepatic activity of Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) was decreased by 59% (P less than 0.05) in SZ-treated rats. Nicotinamide administered prior to SZ prevented the hyperglycemia indicative of SZ-induced diabetes, but had no effect on the decrease in Na+,K(+)-ATPase activity caused by the drug. These results suggest that SZ itself, and not its diabetogenic effect, decreases the BSIF by a mechanism that involves impairment of the biliary electrolyte excretion, which could be the result of the inhibition of the hepatic Na+,K(+)-ATPase activity.

Animals↗
PubMed1992

Cellularity and fibrin mesh properties as a basis for ultrasonic tissue characterization of blood clots and thrombi.

This in vitro study was designed to evaluate the ability of ultrasonic tissue characterization (UTC) based on power spectrum analysis of backscattered radio-frequency echo signals to distinguish two prominent variables of thrombi: cellularity (primarily red cell content) and fibrin-mesh density. Six types of clots simulating thrombus components were prepared by varying red-cell and platelet concentrations and shear forces during clotting. Data were acquired with a linear-array transducer, digitized, and analyzed in terms of slope and intercept parameters obtained from normalized power spectra of radio-frequency echo signals. Increased cellularity and fibrin-mesh density both produced lower slope and higher intercept values, which permitted statistically significant discrimination of cellularity and mesh density in the six types of clots analyzed. Shearing forces and (to a lesser degree) platelet concentrations increased fibrin-mesh density. This study suggests that UTC based upon the power spectrum of echo signals may be used to detect and follow compositional differences that have clinical relevance in the diagnosis and follow-up of thrombi.

Blood Coagulation↗
PubMed1982

Growth in the first four years: I. The relative effects of gender and weight for gestational age at birth.

The growth of 238 small-for-dates (SFD), 246 average-for-dates (AFD) and 241 large-for-dates (LFD) babies was assessed at regular intervals from birth to four years. At all ages, and for both sexes, the mean weight, length or height, and head circumference values for the two extreme groups differed significantly from the AFD group (P less than 0.001). During the first six months actual and relative growth was highest in the SFD group and lowest in the LFD group. With the exception of length in the LFD group it was higher for boys than for girls. Thereafter differences in actual values were slight, while the proportional increases for the three groups were almost identical. Differences from the AFD mixed-sex mean value were plotted for each group and sex combination. Stabilization of the mean trajectories in the two extreme groups occurred at six months for weight and head circumference, but not until 12 months for length. For each child a straight line was fitted on a log scale to these differences from six months (12 months for length) to four years, and analyses of variance of the slopes and intercepts obtained. The sex difference for weight and height gradually decreased, but for head circumference held constant. Estimates of the difference in intercepts of the birthweight groups and sexes showed that within the LFD group the difference in height between boys and girls was much less than in the other two groups. The sex difference for head circumference was slightly larger than the difference between SFD and AFD groups, and twice the difference between the LFD and AFD groups. At the age of four years the mean value for AFD boys was higher than LFD girls (P less than 0.01), and those for SFD boys and AFD girls were almost identical.

Birth Weight↗
PubMed1994

The relationship between auditory brainstem response latencies and behavioral thresholds in normal hearing infants and adults.

The relationship between behavioral thresholds and auditory brainstem response (ABR) latencies for 4 and 8 kHz tone pips were examined in normal-hearing 3-month-olds, 6-month-olds and adults. The latencies of waves I and V and the I-V interval of the ABR were analyzed. A linear latency-intensity function was also fit to each subject's latencies for each wave at several levels. The y-intercept of the latency-intensity function was used as a summary measure of latency to examine behavior-ABR correlations. The pattern of age-related change in behavioral threshold was not closely matched by age-related latency reduction for Wave I, Wave V or the I-V interval. However, 3-month-olds with higher behavioral thresholds had longer Wave V latencies and longer I-V intervals than 3-month-olds with lower behavioral thresholds. There was no significant difference in latency between 6-month-olds or adults with higher thresholds and 6-month-olds or adults with lower thresholds. There was also a significant correlation between the Wave V-Wave I latency-intensity intercept difference and behavioral threshold at both 4 and 8 kHz among 3-month-olds. The correlation was not significant among 6-month-olds or adults. These findings suggest that one of the factors responsible for immature behavioral thresholds at 3 months is related to transmission through the auditory brainstem. Because variability in hearing threshold among normal-hearing adults is low, it is not surprising that behavioral threshold is unrelated to ABR latency in this group. However, the lack of such a relationship among 6-month-olds implies that structures central to the auditory brainstem, either sensory or nonsensory, or both, must be responsible for immature behavioral thresholds after 6 months of age.

Acoustic Stimulation↗
PubMed1991

Another cholesterol hypothesis: cholesterol as antioxidant.

Current emphasis on cholesterol as agency if not cause of human atherosclerosis and subsequent cardiovascular disease ignores the essentiality of cholesterol in life processes. Additionally ignored is the ubiquitous presence of low levels of oxidized cholesterol derivatives (oxysterols) in human blood and select tissues, oxysterols also implicated in atherosclerosis. Whereas such oxysterols may be regarded putatively as agents injurious to the aorta, an alternative view of some of them is here proposed: that B-ring oxidized oxysterols of human blood represent past interception of blood and tissue oxidants in vivo by cholesterol as an ordinary aspect of oxygen metabolism. Such interception and subsequent efficient hepatic metabolism of oxysterols so formed, with biliary secretion and fecal excretion, constitute as in vivo antioxidant system. Whether cholesterol, oxysterols, oxidized lipoproteins, or oxidants in blood, singly or in concert, cause or exacerbate human atherosclerosis remains to be understood.

Antioxidants↗