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Biomedical subjects

J W Hicks

Publications and source records attributed to J W Hicks.

69 records · Page 4Linked to original sources

Effect of sodium butyrate, a differentiating agent, on cell surface glycoconjugates of a human pancreatic cell line.

The effects of sodium butyrate, a differentiating agent, on growth properties and glycoconjugates of a human pancreatic carcinoma cell line (CAPAN-1) were studied. Butyrate caused marked changes of in vitro growth properties including prolongation of doubling time and greatly reduced colony forming efficiency in soft agar. Cell surface labeling revealed significant alterations in proteins and glycoproteins after treatment with sodium butyrate (appearance of glycoproteins of molecular weight 250,000, 220,000, and 70,000; reduction of glycoproteins of 164,000, 148,000, 110,000, and 66,800 sizes; increases in proteins/glycoproteins of 85,000 and 78,000). Metabolic labeling of the cells with [3H]fucose or [3H]galactose revealed that sodium butyrate treatment caused a marked reduction in the fucose-containing neutral glycolipids with six or more carbohydrate side chains and an increase in [3H]galactose-labeled neutral glycolipids, particularly GL-3a, GL-4a, and GL-5a. There was marked reduction in the labeling of a ganglioside with mobility similar to that of GM4 and of sulfogalactosylceramide. An increase in a ganglioside with mobility above GM1 was also caused by butyrate. These data indicate that sodium butyrate may be useful in the identification of differentiation or malignancy-associated glycoconjugate markers of human pancreatic cells.

Butyrates↗

Relationship between respiratory state and intracardiac shunts in turtles.

Injection of radioactively labeled microspheres and blood O2 analysis from central vascular sites was utilized to assess intracardiac shunts in the unanesthetized and unrestrained turtle, Pseudemys scripta, at 15 degrees C. Both methods indicated a simultaneously occurring right-to-left (R-L) and left-to-right (L-R) shunt during ventilation and apnea. During ventilation, the O2 method estimated a R-L shunt of 24%. In contrast, injection of microspheres during ventilation estimated a R-L shunt of 65%, which was significantly greater than the value determined from the O2 method. During apnea, both methods indicated a significantly larger R-L shunt. Estimates of the R-L shunt from O2 analysis were between 60 and 90% of the venous return. The R-L shunt estimated from the O2 content of left aortic arch blood was significantly greater than the value determined from right aortic arch blood. During apnea, the microsphere method estimated a R-L shunt of 79%, which was in the intermediate range calculated by the O2 method using two aortic arches. Our results verify previous reports of significant differences in R-L shunt levels between ventilation and apnea during the normal ventilatory cycle of turtles.

Animals↗

Siphon mechanism in collapsible tubes: application to circulation of the giraffe head.

Controversy exists over the principles involved in determining blood flow to the head of a giraffe, specifically over the role of gravity pressure (pgh) in the collapsible jugular vein in facilitating uphill flow in arteries. This study investigated the pressures within vertically oriented models containing both rigid and collapsible tubes. An inverted U tube was constructed (height = 103 cm) of thick rubber tubing in the ascending limb and collapsible dialysis tubing in the descending limb. Water flow was induced by a variable speed pump maintained at the reservoir level such that the descending limb was partially collapsed. Pressure measurements were made at various levels within the U tube by two methods: 1) with the transducer at same level as the tip of the water-filled catheter and 2) with the transducer at the reservoir level. During flow, the pressure at any point was nearly atmospheric along the length of the descending limb. Such methods of obtaining pressure indicated that the pressure gradient within the partially collapsed descending limb was the sum of viscous flow pressure (P1-P2 of Poiseuille) and gravitational pressure (pgh). To study the facilitatory effect of a siphon, the descending limb was compared with a horizontally placed limb (length = 100 cm), and the flow was kept constant. Calculations of hydraulic "work" (pressure x flow) indicated that with a partially collapsed descending limb, work of the pump was reduced by 15% compared with uphill flow to the elevated horizontal position. It is concluded that the siphon mechanism operates in a partially collapsed descending limb of a siphon loop.

Animals↗

Effect of temperature on chemical control of ventilation in Mexican black iguanas.

The impact of temperature on the chemical control of respiration in the Mexican black iguana Ctenosaura pectinata was examined by measuring ventilatory responses to graded hypoxia with and without 2.9% inspired CO2 at 25, 30, and 35 degrees C. Black iguanas increased pulmonary ventilation in response to hypoxia by increasing both tidal volume and respiratory frequency. Breathing 2.9% CO2 stimulated an increased pulmonary ventilation primarily through increases in tidal volume. The fractional O2 concentration at which ventilation began to increase (hypoxic threshold) varied with temperature, increasing from 0.067 at 25 degrees C to 0.085 at 30 degrees C and 0.112 at 35 degrees C. At 35 degrees C, breathing 2.9% CO2 promoted a further, although statistically insignificant, shift in the ventilatory hypoxic threshold to approximately 0.130 fractional inspired O2 concentration. A "gasping" ventilatory pattern was also observed, the frequency of which increased with progressive hypoxia and increasing temperature. These results suggest that the chemical control of ventilation in this lizard is susceptible to changes in temperature, although the mechanism underlying the temperature sensitivity remains obscure.

Animals↗

Analysis of intracardiac shunting in the lizard, Varanus niloticus: a new model based on blood oxygen levels and microsphere distribution.

The central sites of the cardiovascular system (right and left aortic arches, RAo and LAo, pulmonary artery, PA, and right and left atria, RAt and LAt) were chronically and non-occlusively cannulated for an analysis of intracardiac shunting in Varanus niloticus. Oxygen partial pressure (PO2) and oxygen concentration (CO2) were significantly higher in right aortic blood than values determined in left aortic blood. The difference was larger in animals acclimated to 25 degrees C (RAo CO2 = 4.5 +/- 1.00 vol %, LAo CO2 = 3.8 +/- 1.14, X +/- SD, n = 19) than at 35 degrees C (RAo CO2 = 5.8 +/- 1.24, LAo CO2 = 5.4 +/- 1.35, n = 18) (P less than 0.001 for both temperatures, paired t-test). These data are explained by a new model describing the differential shunting patterns of the two aortae in addition to the conventional overall right-to-left and left-to-right shunt fractions. This model was solved on the basis of blood gas data collected by simultaneous multiple-site gas analysis, together with data on the differential blood flow in the central vascular system, collected by application of the microsphere method. At 35 degrees C both right-to-left and left-to-right shunts were relatively small (about 9%), with the right-to-left shunt fraction directed exclusively into the left aorta. Thus right aortic blood represented left atrial blood, whereas left aortic blood was composed of 80% left atrial and 20% right atrial blood. Ninety percent of the pulmonary arterial blood was derived from the right atrium and 10% from the left atrium. At 25 degrees C the composition pattern of effluent blood for each vessel was similar, the absolute flow distribution, however, was different from that at 35 degrees C. These findings are discussed with respect to their significance and compatibility with the wash-out shunt model.

Animals↗

Effects of sodium butyrate on human colonic adenocarcinoma cells. Induction of placental-like alkaline phosphatase.

We have examined the effects of the "differentiating agent," sodium butyrate, on the induction of alkaline phosphatase in human colonic tumor cell line LS174T. Culture of these cells in the presence of 2 mM butyrate caused this activity to increase from less than 0.0001 unit/mg of protein to greater than 0.7 unit/mg of protein over an 8-day period. This induction proceeded in a nonlinear fashion with a lag time of 2-3 days occurring before enzymatic activity began to rise. These increases in activity were accompanied by elevations in the content of a placental-like isozyme of alkaline phosphatase as demonstrated by "Western" immunoblots. Dome formation, indicative of differentiation in cultured cells, also required 3 days treatment with butyrate before becoming evident. The rate of biosynthesis of the enzyme, examined using metabolic labeling with L-[35S]methionine and immunoprecipitation, was found to increase continuously between days 2 and 6 of butyrate treatment. "Northern" blot analysis indicated that treatment of these cells with butyrate caused greater than 20-fold induction of a 2700-base mRNA that hybridized to a cDNA probe for placental alkaline phosphatase. The mRNA for alkaline phosphatase produced by these cells upon butyrate treatment was approximately 300-400 bases smaller than the mRNA for alkaline phosphatase found in placenta. Human small intestine also contained two mRNAs that hybridized relatively weakly with the placental alkaline phosphatase probe. These results indicate that a placental alkaline phosphatase-like protein and mRNA are induced by butyrate in LS174T cells with a time course consistent with cellular differentiation preceding induction.

Adenocarcinoma↗

Voice stress evaluators and lie detection.

Proponents of vocal stress analysis systems argue that they are able to detect spoken deception by analysis of "stress" in the voice signal. Presumably, they do so by examining traces made by laryngeal microtremors which, they claim exist in the voice, are associated with stress, and ultimately are associated with lying. However, most research that seeks to identify the relationships between microtremors and laryngeal function has produced negative results, and data on the ability of voice analyzers to detect stress from speech--or to identify spoken deception--have been negative or "mixed" in nature. Since perspectives based on available results leave a number of questions unanswered, a series of experiments has been undertaken. The first was focused on the basic acoustic/temporal correlates of stress in voice (the subject of an earlier report), the second on examination of stress by commercial voice analyzers, and the third on the detection of relatively high-risk lies by this same type of voice analysis procedure. It was found that correct stress/nonstress identifications occurred only at chance levels; the lie/nonlie identification scores were quite similar with professional "examiners" performing at about the same level of accuracy as other auditors. The following review is divided into two parts: a history of the controversy and a presentation of the two cited experiments.

Adult↗

An acoustic approach to diver navigation.

Three experiments were carried out to assess the capability of divers to localize acoustic signals underwater and to navigate by them. In the first experiment, divers attempted to determine the correct distance to several underwater transducers projecting acoustic stimuli on a horizontal plane. The second experiment consisted of two related studies where the diver/subjects attempted to discover which of many possible stimuli would produce the most robust perception of underwater "sound movement," or the Underwater Auditory Phi Phenomenon (UAPP). A third experiment consisted of navigational swims by divers; the acoustic stimuli utilized were based on those identified in prior experiments as the most preferred. The results demonstrated that divers are able to discriminate among signals emanating from acoustic sources at various distances underwater and to do so at levels well above chance. Second, divers judged 500-Hz square waves to be the signal which best facilitated an acceptable UAPP; thermal noise and 1-kHz square waves followed in that order. However, these differences were only slight and, in practice, divers maintained that the noise signal was the most useful. Third, it was found that divers apparently can effectively navigate by means of auditory signals alone--at least within certain limits. Finally, a significant decrease in the discrimination abilities of divers for frequencies above 6 kHz suggests that intensity cues may not be as robust as time-of-arrival information with respect to underwater sound localization.

Acoustic Stimulation↗

Temperature regulation in lizards: effects of hypoxia.

Temperature regulation during external (lowered lung PO2) and internal hypoxia (anemia) was examined in four species of lizards. Exposure to a hypoxic gas mixture in a thermogradient resulted in the animals lowering their selected (preferred) body temperature. A 50% reduction in the O2 carrying capacity of the blood also reduced the selected body temperature. Lizards "shuttle" when forced to select a temperature either above or below their normal selected temperature. Exposure to hypoxia decreases the upper and lower exit temperatures during shuttling. Furthermore, a decrease in the inspired O2 causes the rate of heating to no longer exceed the rate of cooling as is normal. The behavioral reduction of body temperature and the altered neural and physiological aspects of temperature regulation appear to be generalized responses to impaired O2 transport and not PO2 per se. The reduced body temperature, by lowering metabolic demand, provides an effective, even life-saving, adaptation to hypoxia.

Anemia↗

Voice fundamental frequency levels of divers in helium-oxygen speaking environments.

Divers under hyperbaric conditions experience a marked deterioration in speech intelligibility. Included among the possible features that contribute to speech degradation is change/distrotion of speaking fundamental frequency (SFF). Based on the physics of the environment and the physiology of the diver, it would not be expected that SFF would change as a function of varying helium-oxygen pressure conditions. However, in an earlier pilot study, a rise in SFF was found with increases in depth. To test this hypothesis, and to expand the previous limited findings, a large number of U. S. Navy divers were studied. The diver/subjects produced speech samples at the surface and at depths of 200, 450, and 600 fsw in helium-rich environments. The resulting data revealed increases in fundamental frequency to the 450-fsw depth and a subsequent decrease at 600 fsw; further analysis, however, based on data transforms, showed a more linear increase in SFF. From other observations, it was judged that behavioral rather than physical conditions were the primary cause of these SFF shifts; specifically, they appear to have resulted from divers' attempts to speak more intelligibly.

Atmosphere Exposure Chambers↗

Human monkeypox.

Between October 1970 and May 1971, six cases of human infection with monkeypox virus were identified in Liberia, Nigeria, and Sierra Leone. Four of the cases were confirmed by virus isolation and two were diagnosed on the basis of epidemiological and serological investigations. All the cases occurred in unvaccinated individuals.Post-infection serological studies showed high haemagglutination-inhibition and neutralizing titres to pox group virus in four of the cases. Repeated challenge vaccination of all cases with potent smallpox vaccine resulted in equivocal reactions.In all, 24 susceptible household contacts were exposed to the infected cases, but none developed disease. All the contacts subsequently responded to vaccination with a primary reaction, thus confirming their susceptibility and ruling out asymptomatic infection.

Adult↗

Pulmonary gas exchange during intermittent ventilation in the American alligator.

The present study characterized pulmonary gas exchange in the American alligator, Alligator mississipiensis during ventilation and apnea at a body temperature (Tb) of 25 degrees C. Pulmonary gas exchange parameters were measured on a breath-by-breath basis utilizing a computer-assisted data acquisition system. In addition, paired blood samples were analyzed from left and right atrium during ventilation and voluntary apneas (1, 2, 5 and 10 min). Measurements of lung PO2 and PCO2 indicated that as apnea progressed, CO2 flux into the lung decreased rapidly while O2 was continuously removed at a constant and steady rate. The reduction in VCO2 resulted in a decrease in R (less than 0.4). Blood gas measurements indicated that the pulmonary arterial-pulmonary venous PCO2 difference, (Ppa-Ppv)CO2 was 4.9 +/- 0.9 mmHg during ventilation, decreased and became negative within 2 min of apnea, reaching -3.9 +/- 0.6 mmHg after 10 min. It is postulated that during apnea the Haldane effect accounts for both the blood gas behavior across the lung and insures a continued CO2 flux into the lung during apnea.

Alligators and Crocodiles↗

Isolation and structural characterization of insulin, glucagon and somatostatin from the turtle, Pseudemys scripta.

The chelonians occupy an important position in phylogeny representing a very early branching from the ancestral reptile stock. Hormonal polypeptides in an extract of the pancreas of the red-eared turtle were purified to homogeneity by reversed phase HPLC and their primary structures were determined. Turtle insulin is identical to chicken insulin. Turtle glucagon differs from chicken glucagon by the substitution of a serine by a threonine residue at position 16 and from mammalian glucagon by an additional substitution of an asparagine by a serine residue at position 28. Turtle pancreatic somatostatin is identical to mammalian somatostatin-14. The crocodilians are phylogenetically much closer to the birds than are the chelonians. Alligator insulin, however, contains three amino acid substitutions relative to chicken insulin. Thus, caution is required when inferring phylogenetic relationships based upon a comparison of amino acid sequences of homologous peptides.

Amino Acid Sequence↗

Cardiovascular regulation during anoxia in the turtle: an in vivo study.

This study describes the integrated cardiovascular response of instrumented turtles to acute anoxic exposure (approximately 2 h) and also determines the factors that regulate these responses. Trachemys scripta were chronically implanted with ultrasonic blood flow probes for the measurement of total pulmonary and systemic blood flows and heart rate. In addition, catheters were implanted into the right aortic arch for the measurement of systemic blood pressure, arterial blood gases, and pH. Animals were free to swim within an aquarium but could only breathe within a small chamber located at the surface. Cardiovascular variables were continuously monitored during normoxia, 2 h of anoxia, and during recovery at normoxia. In addition, some animals were treated with atropine or epinephrine during the anoxic exposure. During the onset of nitrogen breathing there was an increase in ventilation frequency, heart rate, pulmonary blood flow, and systemic blood flow and the development of a net left-to-right cardiac shunt. These changes lasted up to 1 h, followed by bradycardia (heart rate was reduced by 50% from control values) and the development of a large net right-to-left shunt (approximately 80% of the total cardiac output). These changes lasted the duration of the anoxic exposure and were rapidly reversed on return to a normoxic environment. Injections of epinephrine during anoxia had no effect on heart rate, pulmonary blood flow, or systemic blood flow. In contrast, injection of atropine during anoxia resulted in an increase in the heart rate and systemic blood flow, suggesting that the anoxic cardiac response is partially mediated through cholinergic mechanisms.

Acute Disease↗