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Biomedical subjects

D A Williams

Publications and source records attributed to D A Williams.

At least 163 records · Page 9Linked to original sources
PubMed1996

Beneficial effects of voluntary wheel running on the properties of dystrophic mouse muscle.

Effects of voluntary exercise on the isometric contractile, fatigue, and histochemical properties of hindlimb dystrophic (mdx and 129ReJ dy/dy) skeletal muscles were investigated. Mice were allowed free access to a voluntary running wheel at 4 wk of age for a duration of 16 (mdx) or 5 (dy/dy) wk. Running performance of mdx mice (approximately 4 km/day at 1.6 km/h) was inferior to normal mice (approximately 6.5 km/day at 2.1 km/h). However, exercise improved the force output (approximately 15%) and the fatigue resistance of both C57BL/10 and mdx soleus muscles. These changes coincided with increased proportions of smaller type I fibers and decreased proportions of larger type IIa fibers in the mdx soleus. The extensor digitorum longus of mdx, but not of normal, mice also exhibited improved resistance to fatigue and conversion towards oxidative fiber types. The dy/dy animals were capable of exercising, yet ran significantly less than normal animals (approximately 0.5 km/day). Despite this, running increased the force output of the plantaris muscle (approximately 50%). Taken together, the results showed that exercise can have beneficial effects on dystrophic skeletal muscles.

Aging↗
PubMed1996

Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers.

Clenbuterol, a beta 2-adrenoceptor agonist, has therapeutic potential for the treatment of muscle-wasting diseases, yet its effects, especially at the single-fiber level, have not been fully characterized. Male C57BL/10 mice were allocated to three groups: Control-Treated mice were administered clenbuterol (2 mg.kg-1. day-1) via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) in addition to receiving clenbuterol; and Control mice were sedentary and untreated. Contractile characteristics were determined on membrane-permeabilized fibers from the extensor digitorum longus (EDL) and soleus muscles. Fast fibers from the EDL and soleus muscles of Treated mice exhibited decreases in Ca2+ sensitivity. Endurance exercise offset clenbuterol's effects, demonstrated by similar Ca2+ sensitivities in the Trained-Treated and Control groups. Long-term clenbuterol treatment did not affect the normalized maximal tension of fast or slow fibers but increased the proportion of fast fibers in the soleus muscle. Training increased the proportion of fibers with high and intermediate succinate dehydrogenase activity in the EDL and soleus muscles, respectively. If clenbuterol is to be used for treating muscle-wasting disorders, some form of low-intensity exercise might be encouraged such that potentially deleterious slow-to-fast fiber type transformations are minimized. Indeed, in the mouse, low-intensity exercise appears to prevent these effects.

Adrenergic beta-2 Receptor Agonists↗
PubMed1996

Endothelium-medicated control of the coronary circulation. Exercise training-induced vascular adaptations.

This review discusses the role of the endothelium in the regulation of coronary vascular function. The role of endothelium-mediated mechanisms at rest, during exercise, in exercise training-induced adaptations of coronary function and in the presence of coronary heart disease (CHD) are examined. Mechanisms of control of coronary blood flow are briefly discussed with emphasis on endothelium-mediated control of vascular resistance. The concept that the relative importance of vascular control mechanisms differs as a function of position along the coronary arterial tree is developed and discussed. Metabolic, myogenic and endothelium-mediated control systems contribute in parallel to regulating coronary blood flow. The relative importance of these mechanisms varies throughout the coronary arterial tree. Endothelium-dependent vasodilation contributes to maintenance of resting coronary blood flow but the endothelium's role in dilation of small resistance arteries, thereby increasing coronary blood flow during exercise, remains in question. In contrast, the endothelium plays an essential role in dilation of the conduit coronary arteries during exercise. Atherosclerosis and CHD convert this exercise-induced dilation to a vasoconstriction, apparently due to endothelium dysfunction. Long term increases in physical activity and exercise training alter the control of coronary blood flow. Adaptations in endothelium-mediated control play a role in these changes. However, the effects of the mode, frequency, and intensity of exercise training bouts and duration of training on adaptive changes in endothelial function have not been established. The role of the endothelium in control of the permeability characteristics of the exchange vessels in the coronary circulation is discussed. Current evidence indicates that vascular permeability is a dynamic characteristic of the vessel wall that is controlled, at least in part, by endothelium-dependent phenomena. Also, preliminary results indicate that exercise training alters microvessel permeability and the control of permeability in the coronary circulation. Further research is needed to provide clarification of the effects of exercise training on coronary endothelial control of vascular resistance and vascular permeability in atherosclerosis and CHD.

Adaptation, Physiological↗
PubMed1996

A shear stress component to the modulation of capillary hydraulic conductivity (Lp).

OBJECTIVE: Two major factors that determine transcapillary exchange are Starling forces and hydraulic conductivity (Lp) of capillary walls. Although chemical stimuli alter Lp, the influence of mechanical stimuli has been neglected. Therefore, we tested the hypothesis that the Lp of intact capillaries would increase with the magnitude of changes in shear stress presented to each capillary. METHODS: Capillaries (n = 26) in the mesentery of pithed frogs (n = 23) were cannulated at 30 cm H2O (average in situ pressure = 9.2) to alter shear stress. For the calculation of shear stress, velocities of both frog red blood cells (RBC) and human RBC in the pipette solution were measured in each capillary before and after cannulation, respectively. Lp was assessed 2 min after cannulation. RESULTS: Venular capillaries only responded to the changes in shear stress. The magnitude of the changes in shear stress correlated positively with the values for capillary Lp (Kendall's tau = 0.56; p = 0.02). CONCLUSIONS: While Starling forces influence the movement of fluid by acting perpendicular to the long axis of capillaries, shear stress acts in a plane tangential to the capillary walls and appears to alter capillary Lp. In addition to chemical stimuli, the mechanical stimulation of capillaries can alter the barrier itself and consequently alter filtration rate.

Animals↗
PubMed1996

Isolation and characterization of alpha 1-protease inhibitor from canine plasma.

OBJECTIVE: To improve a previously described purification process by producing a higher yield and purity of alpha 1-protease inhibitor (alpha 1-PI) from canine plasma. ANIMALS: Plasma pool from 10 clinically normal male dogs. PROCEDURE: Canine alpha 1-PI was purified by use of ammonium sulfate precipitation, ion-exchange chromatography, and 3 affinity chromatographic procedures: concanavalin A-Sepharose, thiol, and hemoglobin-Sepharose. Characterization was performed by gel electrophoresis, isoelectric focusing, and immunoblot analysis. The N-terminal amino acid sequence was obtained by use of the Edman degradation method and a gas amino acid sequencer. RESULTS: Canine alpha 1-PI was purified with a yield of approximately 7% and a 54-fold increase in specific inhibitory activity. The inhibitor had a molecular weight of 59,000 and had 2 major patterns after isoelectric focusing: fast and intermediate in homozygous and/or heterozygous forms. Edman degradation revealed glutamic acid as the starting amino acid from the N-terminal sequence. Homologies of the N-terminal sequence of canine alpha 1-PI with those of sheep, horse, and human alpha 1-protease inhibitors were 54, 46, and 41%, respectively. CONCLUSIONS: Canine protease inhibitor is analogous to the alpha 1-protease inhibitors of sheep, human beings, and mice in terms of molecular weight, amino acid composition, and inhibitory activity against trypsin. Although the method described had a yield of 7%, the final product retained inhibitory activity and was pure. CLINICAL RELEVANCE: The availability of pure canine alpha 1-PI, as well as the specific antibodies, will facilitate studies on the fecal excretion and structural heterogeneity of this protein in dogs with naturally acquired protein-losing enteropathy.

Amino Acid Sequence↗
PubMed1996

Interleukin-11 prevents apoptosis and accelerates recovery of small intestinal mucosa in mice treated with combined chemotherapy and radiation.

Previous studies have shown that acute injury to rodent small intestinal mucosa as a result of either chemotherapy or radiation is caused by a combination of high-frequency cell death caused by apoptosis, continued migration of epithelial cells from the intestinal crypts toward the villi, and absence of adequate compensatory mitotic activity in the crypt bases. Recently, we have shown that IL-11, a novel multifunctional bone marrow stromal-derived growth factor, could stimulate rapid repair of small intestinal villous structures in mice treated with combined radiation and chemotherapy by increasing the mitotic index of crypt cells. To further clarify the biological mechanism responsible for its protective action, we used a similar experimental model to evaluate whether IL-11 could reduce the high frequency of apoptosis observed after cytoablative treatment. In the present study, 78 C3H/HeJ mice received 5-fluorouracil at 150 mg/kg body weight intraperitoneal injection 3 days before 7.0-Gy total body irradiation. The animals received IL-11 250 microg/kg body weight/day divided into two equal doses or vehicle control by subcutaneous injections beginning on the same day of irradiation within 1 hour of the end of the dose. The mice killed on Days 1, 2, and 5 after cytoablative treatment were autopsied, the small intestine was processed for histologic examination, and the mitotic index and other parameters were measured, including the expression of the proliferating cell nuclear antigen and of the p53 protein. Apoptosis was detected by a nonisotopic in situ DNA end-labeling technique applied to the same histologic sections. The cytoablative treatment caused marked degenerative changes in the small intestinal mucosa, including shortening of the villi and damage to the crypt cells. The degenerative changes, which included nuclear fragmentation with formation of apoptotic bodies, increased expression of proliferating cell nuclear antigen, and strong expression of p53 was seen in mice killed on Days 1 and 2 after cytotoxic treatment. IL-11 administration resulted in a partial suppression of apoptosis, as shown by a reduced number of crypt cells stained with in situ DNA end-labeling for fragmented DNA. In addition, IL-11 treatment was associated with an increase in the frequency of mitosis and proliferating cell nuclear antigen expression in crypt cells as compared with the vehicle treated mice. Morphometric analysis of intestinal villi and crypt depth showed increased villus length and decreased crypt to villus ratio after IL-11 treatment. These results indicate that IL-11 can exert a potent effect on the recovery of the small intestinal mucosa of mice by its combined effects on proliferation and apoptosis of crypt cells. IL-11 may thus have potential clinical applications in limiting the intestinal toxicity that is associated with cytotoxic therapies.

Animals↗
PubMed1996

Development and validation of a radioimmunoassay for feline trypsin-like immunoreactivity.

OBJECTIVE: To develop and validate a radioimmunoassay for feline trypsin-like immunoreactivity (fTLI). PROCEDURE: A double antibody radioimmunoassay for determination of fTLI was developed, using feline trypsin purified from feline pancreatic tissue antiserum against feline trypsin raised in New Zealand White rabbits, and a commercially available precipitation solution. This assay was validated by determining detection limit, linearity, accuracy, and intra- and interassay variabilities. A control range was determined from samples of 21 clinically normal cats. RESULTS: The detection limit for fTLI in this assay was 1.9 micrograms/L. The linearity of the assay was evaluated by testing dilutional parallelism. Observed/expected values ranged between 95 and 127%. The accuracy of the assay was tested by measuring recovery of added trypsin. Observed/expected values ranged from 99 to 114%. Intra-assay variability ranged between 3.0 and 9.4%, and interassay variability ranged between 4.0 and 8.2%. The control range for serum fTLI was determined to be 17.1 to 48.6 micrograms/L. CONCLUSION: The assay for fTLI described here is sensitive, linear, accurate, precise, and reproducible. CLINICAL RELEVANCE: This assay may be of use for the diagnosis of exocrine pancreatic diseases in cats. Preliminary results of such research have been promising, and further clinical studies are in progress.

Animals↗
PubMed1996

A novel method of myeloablation to enhance engraftment of adult bone marrow cells in newborn mice.

This report describes the successful development of a transplantation model in which we engrafted adult murine bone marrow hematopoietic cells in congenic day-old murine pups. Newborn animals conditioned with high doses (> or = 7.0 Gy) of total-body irradiation (TBI) demonstrated severe growth retardation and untoward effects on the developing central nervous system. Newborn pups conditioned with a sublethal dose (5.0 Gy) of TBI, however, achieved normal growth and development up to 6 months posttransplantation, and donor type hematopoietic cell reconstitution exceeded 50% in these animals. A second conditioning regimen, comprising one or two doses of busulfan (15 mg/kg) administered intrapartum, resulted in significant myelosuppression in untransplanted newborn pups. This second regimen was associated, however, with engraftment and full multilineage reconstitution of the conditioned newborn recipient animals with adult bone marrow cells, and the engrafted pups grew and developed without apparent defect. A third conditioning regimen combining a single dose of busulfan with sublethal TBI also permitted engraftment and full multilineage reconstitution of the recipient animals. Thus, successful transplantation of hematopoietic cells into newborn recipient mice may be achieved without significant morbidity if a specific conditioning regimen is employed.

Animals↗
PubMed1996

Drug stability and compatibility in oncology care.

Infusional chemotherapy has been increasingly used based upon the fact that most drugs have a relatively short half-life following bolus exposure, and increasing the available drug concentration over time may maximize the antitumor effect. As a practical matter, the application of infusional chemotherapy especially in an ambulatory setting, absolutely requires that the individual antineoplastic agents be stable in solution at room temperature (or at body temperature for implanted pump systems) and that the drugs in the infusion (including antiemetics) be compatible. The capacity to mix antineoplastic agents and antiemetics (also colony-stimulating factors) in a single solution facilitates infusional combination chemotherapy. Technologic advances are on the horizon which will provide the capability of administration of multiple drugs through a single access site to allow one to utilize a single delivery source obviating the need for admixtures of drugs. However, in the interim, admixtures represent the optimal method for the delivery of multi-agent chemotherapy in the setting in which continuous infusional drug delivery for 24 hours or more is employed. The goal of continuous infusion cancer chemotherapy is to ensure delivery of an unaltered cytotoxic drug, avoiding situations that could affect the stability of the infusion admixture. With cancer chemotherapy infusion therapy being administered through oncology clinics without the benefits of a pharmacist, the nurse plays a pivotal role in the preparation of the infusion, supervision of the patient, and when applicable in providing counseling on the proper storage, handling of the cytotoxic drugs, and disposal of contaminated infusion materials. Thus, by optimizing the integrity of the chemotherapeutic infusion, the patient achieves maximum benefits of cancer chemotherapy and the level of success anticipated with oncology care. The nurse may also be involved with clinical studies involving the preparation of other combinations of infusional chemotherapy including antiemetics and colony-stimulating factors, requiring integrity of the infusion to incompatibility and instability. In order to avoid failure of the infusion through improper preparation or reconstitution of the infusion or improper storage conditions and the resulting unnecessary waste and disposal expenses, the nurse needs to be fully aware of the factors affecting the stability and compatibility of the infusion and to interact with other health professionals and the literature for the critical information related to maintaining the integrity of the cancer chemotherapy infusion. "Good intentions without good communication equals potential disaster."

Ambulatory Care↗
PubMed1995

Murine embryonic yolk sac cells promote in vitro proliferation of bone marrow high proliferative potential colony-forming cells.

To examine the influence of the hematopoietic microenvironment on hematopoietic cell proliferation and differentiation during the yolk sac phase of hematopoiesis, we have recently established cell lines from embryonic yolk sac visceral endoderm (YSE) and mesoderm (YSM). In the present experiments, we compared in vitro growth of adult murine bone marrow high proliferative potential colony-forming cells (HPP-CFC) in coculture with YSE- and YSM-derived or adult bone marrow stromal cell lines. Whereas both yolk sac-derived and adult stromal cell lines supported the proliferation of HPP-CFC during coculture, YSE- and YSM-derived cells stimulated a significant increase in total HPP-CFC compared with adult bone marrow stromal cell lines. Conditioned media from both YSE- and YSM-derived cell lines also stimulated the growth of HPP-CFC in vitro, but only in combination with exogenous recombinant hematopoietic growth factors. Although multiple hematopoietic growth factor mRNAs were detected in the yolk sac-derived cells by polymerase chain reaction, only macrophage colony-stimulating factor (M-CSF) activity was detected in conditioned media using an enzyme-linked immunosorbent assay. A neutralizing polyclonal antibody against M-CSF did not diminish the YSE- or YSM-derived cell line conditioned media promotion of HPP-CFC colony formation. These results suggest that murine yolk sac-derived cell lines produce a novel soluble factor(s) that recruits primitive bone marrow hematopoietic cells to grow in vitro in response to a combination of hematopoietic growth factors.

Animals↗
PubMed1995

Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures.

Interleukin-11 (IL-11) is a bone marrow microenvironment-derived growth factor with pleiotropic effects on a variety of hematopoietic cells. To more accurately assess the effects of IL-11 on stem and progenitor compartments within the hematopoietic microenvironment (HM), we added recombinant human (rh) IL-11 to human and murine long-term bone marrow cultures (LTMC) and analyzed primitive (high proliferative potential-colony forming cells [HPP-CFC], long-term culture-initiating cells [LTC-IC], and long-term reconstituting stem cells) and progenitor (day 12 colony forming unit-spleen [CFU-S12], colony forming unit-megakaryocyte [CFU-Mk] and colony forming unit-granulocyte/macrophage [CFU-GM]) compartments throughout the duration of the cultures. rhIL-11 (100 ng/mL) added twice weekly resulted in significantly increased nonadherent (NA) cellularity, CFU-GM, and CFU-Mk production in human LTMC. Addition of rhIL-11 to murine LTMC was associated with a 5- to 40-fold increase in CFU-GM and a four- to 20-fold increase in day 12 CFU-S in NA cells. However, IL-11 had no significant effect on total HPP-CFC concentration and decreased the size of the more primitive stem/progenitor compartment as evidenced by both decreased LTC-IC frequency in human LTMC and decreased frequency of long-term reconstituting stem cells in murine LTMC. These data suggest that IL-11 may increase commitment of stem cells into a multipotential progenitor compartment.

Animals↗
PubMed1995

Retrovirus-mediated expression of a DNA repair protein in bone marrow protects hematopoietic cells from nitrosourea-induced toxicity in vitro and in vivo.

Severe and delayed myelosuppression is a major side effect encountered with the clinical use of nitrosourea-type chemotherapeutic drugs. The DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) has been shown to repair nitrosourea-induced DNA damage. We therefore investigated the effect of expressing MGMT in hematopoietic cells (via retrovirus-mediated gene transfer) on nitrosourea-induced toxicity. A retroviral vector (N2/ZipPGK-MGMT) expressing the human MGMT cDNA from the phosphoglycerate kinase promoter was constructed. Infection of murine bone marrow with the N2/ZipPGK-MGMT retrovirus significantly increased the survival of murine bone marrow-committed progenitor cells following in vitro exposure to N-N'-bis(2-chloroethyl)-N-nitrosourea (BCNU, carmustine). MGMT gene transfer also protected murine hematopoietic cells in vivo in a murine model of BCNU-induced myelosuppression. The infusion of 4-6 x 10(6) N2/ZipPGK-MGMT-transduced bone marrow cells into mice every 2 weeks significantly increased peripheral leukocyte counts, platelet counts, and hematocrits compared to infusions of mock-infected bone marrow cells. In addition, bone marrow-committed progenitor cells from some recipient animals demonstrated increased resistance to BCNU in vitro when analyzed 2.5 months after initial treatment. The integration of the N2/ZipPGK-MGMT provirus in the spleen DNA from these animals correlated with committed progenitor cell resistance to BCNU. These data suggest that MGMT expression in hematopoietic progenitor and precursor cells protects against nitrosourea-induced toxicity and that gene transfer may prove useful in attempts to reduce nitrosourea-induced myelosuppression in the clinical setting.

3T3 Cells↗
PubMed1995

Membrane-bound Steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form.

Alternative splicing of exon 6 results in the production of two isoforms of Steel factor (SLF): the membrane-bound and soluble forms. To investigate differences in the kinetics of c-kit tyrosine kinase activated by these two isoforms, we used a stromal cell line (SI/SI4) established from SI/SI homozygous murine embryo fetal liver and its stable transfectants containing either hSCF248 cDNA (including exon 6; secreted form) or hSCF220 cDNA (lacking exon 6; membrane-bound form) as the source of each isoform. Interaction of factor dependent myeloid cell line MO7e with stromal cells producing either isoform resulted in activated c-kit tyrosine kinase and induction of the same series of tyrosine phosphorylated cellular proteins in MO7e cells. However, SI4-h220 (membrane-bound form) induced more persistent activation of c-kit kinase than SI4-h248 (soluble form) did. Flow cytometric analysis and pulse-chase studies using [35S]methionine showed that SI4-h248 induced rapid downmodulation of cell-surface c-kit expression and its protein degradation in MO7e cells, whereas SI4-h220 induced more prolonged life span of c-kit protein. Addition of soluble recombinant human SLF to SI4-h220 cultures enhanced reduction of cell-surface c-kit expression and its protein degradation. Because the kinetics of c-kit inactivation strikingly fits with the protein degradation rates of c-kit under the conditions described above, rapid proteolysis of c-kit protein induced by soluble SLF stimulation may function as a "turn-off switch" for activated c-kit kinase.

Alternative Splicing↗
PubMed1995

The use of umbilical cord blood as a cellular source for correction of genetic diseases affecting the hematopoietic system.

Human umbilical cord blood contains abundant primitive and committed hematopoietic progenitors and has been used as an alternative source of reconstituting hematopoietic stem cells. Recent advances in the understanding of molecular aspects of multiple diseases and improvements in technology associated with prenatal diagnosis now allow the in utero identification of many genetic diseases affecting the hematopoietic system. Advances in technology raise the potential for genetic correction and subsequent transplantation of autologous cord and placental blood hematopoietic stem cells into affected patients prior to expression of the disease phenotype. This review will summarize the recent data on advances in prenatal diagnosis, characterization of the biology of cord blood stem cells, and efforts at developing methods for genetic transduction of cord blood hematopoietic stem/progenitor cells.

Animals↗
PubMed1995

Analysis of Ca2+ and Sr2+ activation characteristics in skinned muscle fibre preparations with different proportions of myofibrillar isoforms.

To understand how the coexistence of fast and slow contractile and regulatory systems within single skeletal muscle fibres might affect contractile behaviour, fibre segments from the fast-twitch extensor digitorum longus and predominantly slow-twitch soleus muscle of the adult rat were tied together, either in parallel or in series, and then activated in Ca(2+)- and Sr(2+)-buffered solutions. Experimental force-pCa and force-pSr relations were compared with theoretical force-pCa and force-pSr curves predicted by a model for composite fibres, which accounted for the coexistence of fast and slow myosin within the contractile unit and enabled an estimate to be made of the relative contribution of fast- and slow-twitch elements within the tied-fibre combinations. The contractile behaviour of a fast-twitch and a slow-twitch muscle fibre tied either in series or in parallel, were compared with the force-pCa and force-pSr data predicted from the composite fibre model. Interestingly, the resultant force-pCa(-pSr) curves of the parallel-tied fibre combinations were well fitted with those predicted by the composite model. However, the experimental force-pCa(-pSr) curves of the series-tied fibres were not well fitted by a composite curve based on the known proportion of fast- and slow-twitch fibre components. A total force-length diagram was devised to take into account changes in the length of the fibre segments tied in series during activation, as well as possible differences in fibre diameter. Using this diagram it was possible to explain accurately the Ca2+ and Sr2+ activation curves of known fast- and slow-twitch segments tied in series. The results from this study are important for the interpretation of contractile data obtained from single muscle fibres exhibiting mixed fast- and slow-twitch contractile characteristics. Such muscle fibres have previously been identified in animals affected by muscular diseases (e.g. dystrophy), in mammalian extraocular muscles and in animals subjected to long-term exercise training.

Animals↗
PubMed1995

A fluorimetric liquid chromatographic method for the determination of propranolol in human serum/plasma.

A simple, rapid, and sensitive fluorimetric-high-performance liquid chromatographic method for the determination of propranolol in human serum/plasma has been developed, without the need for solvent extraction. The procedure required 200 microliters of serum/plasma, and the addition of 1 ml of acetonitrile for protein precipitation followed by vortexing and centrifugation at 10 000 g. The clear supernatant was evaporated to dryness under a stream of nitrogen at 50-60 degrees C, the residue was reconstituted in 100 microliters of methanol, and a 90 microliters portion was injected onto the high-performance liquid chromatograph for propranolol quantitation. Chromatography was accomplished using a Hypersil cyano column, a mobile phase of acetonitrile-aqueous acetic acid (1%) containing 0.2% triethylamine (35:65, v/v) (pH 3.6), a flow rate of 1.5 ml min-1, a fluorescence detector set at an excitation wavelength of 230 nm and an emission wavelength of 340 nm, and using pronethalol as the internal standard. Retention times for pronethalol and propranolol were 7.5 min and 9.5 min, respectively. Standard curves were linear in the range 5-200 ng ml-1. Relative standard deviations for both inter-day and intra-day precision analysis were less than 7% for serum. No interference was observed from endogenous serum/plasma components. Specificity was shown for some, but not all, commonly coadministered drugs tested. The advantages of this method include good precision, low sample volume, good reproducibility and recovery, and high sensitivity.

Adrenergic beta-Antagonists↗
PubMed1995

Forms of inhibition in animal and human learning.

Forms of inhibition were identified in human predictive learning that are qualitatively similar to those identified by P.C. Holland (1984) in rats. When P (positive) signaled the outcome and PN (N = negative) signaled the absence of the outcome, participants learned the discrimination, but the negative cue did not suppress responding to a transfer cue. Post-learning reversal training, in which N was followed by the outcome, did not abolish the original discrimination. These 2 results imply a configural form of inhibition. Negative transfer, which indicated a 2nd, elemental form of inhibition, was observed when neither PN nor N were reinforced during the discrimination stage. Under these conditions, negative transfer and the original discrimination were both abolished by individually pairing N with the outcome. Empirical parallels and differences with the animal conditioning literature are discussed.

Adult↗