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Biomedical subjects

G W Kidder

Publications and source records attributed to G W Kidder.

At least 19 recordsLinked to original sources
PubMed1996

Electromyogram as a measure of heavy metal toxicity in fresh water and salt water mussels.

The response of bivalves to heavy metals and other toxins has usually been determined by observing valve position (e.g., Davenport and Manley 1958; Borcherding 1992). Since mussels close their valves to avoid noxious stimuli, experimental delivery of chemicals is uncertain. To obtain constant results, Preston (1994 and personal communication) employed plastic spacers to hold the valves apart. This obviates the observation of valve position as an index of response, and some other method is required. Electromyography of intact mussels is one such index, and is shown to be a simple, effective and quantitative measurement of activity. Experiments are reported on the effects of added mercury on salt water and fresh water species. Parts of this work have appeared in brief form (Kidder and McCoy 1995).

Animals↗
PubMed1989

Effects of azide on gastric mucose.

Sodium azide, a classical inhibitor of cytochrome oxidase, is an effective inhibitor of gastric acid secretion in bullfrog and skate gastric mucosae at low concentrations. While a portion of the oxygen uptake in these tissues is sensitive to azide (KI less than 2 mM), there remains a large fraction (25-60%) with a KI more than 10 times this value, suggesting the presence of a second oxidase. The spectra of cytochromes c and b change with oxygen-nitrogen alternation in the presence of high azide concentrations which essentially eliminate the reactivity of cytochrome oxidase. In both species two additional components are observed in the spectra. The first has a peak at 590 nm, is not the cytochrome oxidase-CO complex, is fully reactive in the presence of azide and accounts for the asymmetry of the oxidase peak. The second is a component at 557 nm which can only be separated from cytochromes c and b by spectral deconvolution, and seems to react in a manner similar to cytochrome c. It is suggested that the 590 compound may be the alternate cytochrome oxidase.

Animals↗
PubMed1984

Characteristics of cytidine aminohydrolase activity in Trypanosoma cruzi and Crithidia fasciculata.

Cytidine deaminase (cytidine aminohydrolase, 3.5.4.5) is present in Crithidia fasciculata (a mosquito parasite) and in Trypanosoma cruzi (a human pathogen). The enzyme from C. fasciculata deaminated both cytidine and deoxycytidine, the affinity for the former being much lower than the latter. Affinities for both substrates are equal for the T. cruzi enzyme. The production of the enzyme in C. fasciculata was significantly stimulated by the addition of a number of pyrimidine nucleosides (cytidine, uridine, 5-bromouridine, thymidine, orotidine) to the culture media. Only cytidine stimulated enzyme production in T. cruzi. The enzyme from both organisms was unstable in air, even in the frozen state. Stabilization was achieved under anaerobic conditions.

Anaerobiosis↗
PubMed1984

Further studies on sudden potential drop in gastric mucosa.

The sudden potential drop (SPD) with its associated resistance drop, previously noted during anoxia when serosal pH was slightly decreased, can also be produced by substrate deprivation and reversed by addition of substrate. During a critical portion of the response, alternate stable high and low potential difference states can be selected by current pulsing. High Ca2+ in the serosal solution prevents the SPD response, and any condition preventing an SPD response will reverse the post-SPD potential. Although pH 1 mucosal solutions do not damage the tissue, an SPD under these conditions results in permanent loss of secretory activity, apparently due to increased H+ permeability in the post-SPD state. Cl-, Rb+, and urea fluxes are unchanged by the SPD. Since gastric anoxia and mild serosal acidosis might be expected during strong sympathetic stimulation, it is notable that an SPD can be produced in vivo by anoxia or vasoconstrictive drugs under conditions apparently in agreement with the in vitro requirements. This might provide a model system for studies of stress ulcer production. An equivalent circuit model for the SPD is presented, which agrees satisfactorily with the observations.

Aerobiosis↗
PubMed1984

Voltage clamping induces resistance and current-voltage plot changes in frog gastric mucosa.

Changing the potential across the isolated frog gastric mucosa by voltage clamping changes the measured resistance of the tissue in two ways. An immediate change in resistance results from changing the measuring position on the nonlinear current-voltage (I-V) plot. Subsequent to this, the resistance changes slowly with a half-time of about 3 min, a change that is not predicted by a previous model for voltage transients and that implies slow changes in membrane resistance following changes in intracellular ion content. The I-V plot over the range examined shows three breakpoints; changing clamp voltage alters the position of two of these breakpoints as well as the slope of the connecting resistances. The central breakpoint agrees with the potential at zero current and varies with it as the clamp potential is changed, as predicted from a diode model for breakpoint generation.

Animals↗
PubMed1983

Tauroursodeoxycholic acid is less damaging than taurochenodeoxycholic acid to the gastric and esophageal mucosa.

Bile acids are capable of disrupting the gastric and esophageal mucosal barriers and are known to differ in their ability to injure these mucosae. Two bile acids, chenodeoxycholic and its 7-B epimer, ursodeoxycholic, that are being used to dissolve gallbladder stones were evaluated for their damaging effects on experimental preparations of the esophageal (rabbit) and gastric (dog) mucosa. Damage was assessed by measuring indices of mucosal barrier function, including net acid flux, potential difference, and tissue resistance, before and after exposure to the taurine conjugates of these bile acids. In both the esophageal and gastric mucosa, tauroursodeoxycholic acid caused significantly less disruption of barrier function than taurochenodeoxycholic acid. These results demonstrate that minor differences in conjugated bile acid structure can cause major changes in the effects of bile acids on the upper gastrointestinal mucosa and that ursodeoxycholic acid may be the preferred bile acid for oral ingestion to dissolve gallbladder stones.

Animals↗
PubMed1983

An automatic electronic apparatus for generating and recording a ramp stimulus for analgesia testing.

Analgesia testing is conveniently done by applying an electrical stimulus to the tooth pulp of an animal that, in sufficient strength, causes an observable response. The difference in stimulus strength required in treated and control animals is an effective measure of analgesia, if the conditions can be sufficiently standardized. We describe an apparatus which generates a ramp stimulus at a controlled rate, allows accurate determinations of the response voltage with a digital readout, allows holding a reading to determine whether the response is a valid one, and automatically terminates the stimulus when the maximum voltage is reached. This apparatus was constructed from readily available components and can easily be modified to produce various ramp speeds, modulation frequencies, and maximum voltage outputs.

Analgesics↗
PubMed1983

Characterization of dogfish gastric mucosa under hyperbaric conditions.

Using hyperbaric conditions previously shown to give improved oxygen delivery to the chambered dogfish gastric mucosa, experiments were performed to further characterize this tissue under these conditions. Removal of Cl- depressed but did not abolish acid secretion, raised the transepithelial resistance, and caused the potential to become more negative with reference to the mucosal surface. Voltage clamping to -60 mV inhibited secretion significantly; voltage clamping to +60 mV sometimes gave a stimulation. There was no long time-constant transient response to current passage. Under hyperbaric conditions, addition of the normal 350 mM urea content of elasmobranch plasma stimulated secretion. A further increase in partial pressure of oxygen (PO2) above 1.9 atm had no effect on secretion. The current-voltage plot showed two breakpoints, one about -23 mV and a second (not always detectable) at +50 mV; the negative breakpoint was stable as PO2 changed from 0.9 to 1.9 atm. Many of these observations are different from those reported for normabaric tissue and closely resemble those in the isolated frog gastric mucosa.

Animals↗
PubMed1983

Evaluation of in vivo measurement of transesophageal electrical resistance as an indicator of early experimental esophageal mucosal injury.

Experimental esophageal mucosal injury has been characterized by an increase in mucosal permeability to acid and a fall in transmucosal electrical potential difference (PD). We have developed a technique for measuring transesophageal electrical resistance in an in vivo rabbit model of esophageal injury and have performed experiments to assess this parameter as an index of esophageal injury. As expected, tissue resistance varied inversely with mucosal area. The current-voltage plot for the esophagus with or without trypsin, bile, or acid injury remained linear with no "breakpoints." Tissue resistance was compared with standard indices of mucosal injury such as acid flux, PD, and morphologic change in experimental esophageal injury due to acid, bile, and trypsin. Our results show that tissue resistance is more sensitive than either PD or acid flux in detecting early esophageal injury due to low concentrations of acid or trypsin and, as opposed to PD, always showed a persistent, unidirectional change with injury. Thus these data show that in vivo measurement of transesophageal electrical resistance is a useful technique for assessing esophageal mucosal injury, in that it is the most sensitive indicator of esophageal injury we have observed.

Animals↗
PubMed1982

Xanthine phosphoribosyltransferase in Leishmania: divalent cation activation.

Xanthine phosphoribosyltransferase (XPRTase; EC 2.4.4.22) was found in the promastigotes of four species of Leishmania (L. mexicana, L. donovani, L. braziliensis and L. tarentolae). In no case was there any transribosylation from 5-phosphoribosyl-1-pyrophosphate (PRibPP), forming XMP, in dialyzed preparations, unless activated by a divalent cation. Magnesium and zinc were very low in activation efficiency in all cases, while manganese was optimally efficient. Cobalt was essentially equal to manganese for activation of the enzyme from L. mexicana and L. braziliensis but much less efficient for the enzyme from L. donovani and L. tarentolae. Gel filtration profiles of cell extracts of L. mexicana on Sephadex G-200 indicated that the enzymes catalyzing the transribosylation from PRibPP to guanine, hypoxanthine, and xanthine were inseparable. All were eluted near the void volume. The enzyme for adenine transribosylation was clearly separate. When cell extracts of L. mexicana were applied to Sephadex G-100 columns, the activity toward XMP formation from xanthine eluted with the void volume, together with a portion of that for the formation of GMP and IMP from guanine and hypoxanthine. A second peak of HGPRTase (EC 2.4.2.8) eluted somewhat later and was devoid of XPRTase activity. XPRTase from promastigotes of L. mexicana is heat labile, has rather a broad pH optima, and is stable to freezing when protected by nonspecific cell protein (40,000 g supernate as opposed to 100,000 g supernates).

Animals↗
PubMed1982

Enzymatic activities for interconversion of purines in spirochetes.

Enzymatic activities that catalyze the interconversion of purines and purine derivatives were detected in cell extracts of Spirochaeta aurantia, Spirochaeta stenostrepta, Treponema succinifaciens, and Treponema denticola. Phosphoribosyltransferase activities present in cell extracts of each of the four spirochete species functioned in the conversion of adenine, hypoxanthine, and guanine to AMP, IMP, and GMP, respectively. Nucleotidase activities in the extracts mediated the formation of nucleosides from nucleotides. The conversion of adenosine, inosine, and guanosine to the respective purine bases was catalyzed by nucleoside phosphorylase and, in some instances, by nucleoside hydrolase activities. Guanine deaminase activity was found in both S. aurantia and S. stenostrepta, whereas adenosine deaminase activity was detected only in S. aurantia. Adenine deaminase activity in T. succinifaciens extracts was sensitive to O2 and was relatively resistant to heating. Our results indicate that the four species of spirochetes studied possess a broad spectrum of purine interconversion enzymes. It is suggested that these enzymes may function in metabolic processes important for the survival of spirochetes in nutrient-poor natural environments.

Adenosine Deaminase↗
PubMed1981

The in vivo and in vitro action of 4-amino-5-imidazolecarboxamide in trypanosomatid flagellates.

4-Amino-5-imidazolecarboxamide, but not its riboside or ribotide, is inhibitory to the growth of promastigotes of Leishmania donovani, L. braziliensis, L. tarentolae, and L. mexicana, eventually causing cell lysis. Conversely, it is not inhibitory to the growth of epimastigotes of Trypanosoma cruzi. This substituted imidazole proved to be an excellent inhibitor of guanine deaminase from all of the trypanosomatids used in this study, with Ki values in the microM range.

Aminoimidazole Carboxamide↗
PubMed1980

Inhibition of growth and purine-metabolizing enzymes of trypanosomid flagellates by N6-methyladenine.

N6-methyladenine (6-methylaminopurine [6-MA]), a plant growth regulator and a normal constituent of nucleic acids, has been found to inhibit the growth of Trypanosoma cruzi, Leishmania braziliensis, L. donovani, L. tarentolae, L. mexicana, and Crithidia fasciculata. The extent of growth inhibition in these organisms is related to the sensitivity of guanine deaminase (guanine aminohydrolase, EC 3.5.4.3), adenine deaminase (adenine aminohydrolase, EC 3.5.4.2), and adenosine hydrolase and phosphorylase. 6-MA was not an inhibitor of the purine phosphoribosyltransferases. Of the trypanosomid flagellates tested. Trypanosoma cruzi was most susceptible to 6-MA. Neither adenine deaminase (as found in the leishmaniae and C. fasciculata) nor adenosine deaminase (as found in mammalian cells) could be demonstrated in T. cruzi. Guanine deaminase, which is strikingly inhibited by 6-MA in T. cruzi, appears to play a major role in the purine salvage pathway of this organism, as judged from growth experiments and enzyme inhibition studies. Enzyme sensitivities to 6-MA vary greatly depending upon the organism. Rabbit liver guanine deaminase was shown to be insensitive to 6-MA at the concentrations used in this study.

Adenine↗