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Biomedical subjects

R A Johnson

Publications and source records attributed to R A Johnson.

At least 91 records · Page 5Linked to original sources

Automatic activation of phonological information in reading: evidence from the semantic relatedness decision task.

A semantic relatedness decision task was used to investigate whether phonological recording occurs automatically and whether it mediates lexical access in visual word recognition and reading. In this task, subjects read a pair of words and decided whether they were related or unrelated in meaning. In Experiment 1, unrelated word-homophone pairs (e.g., LION-BARE) and their visual controls (e.g., LION-BEAN) as well as related word pairs (e.g., FISH-NET) were presented. Homophone pairs were more likely to be judged as related or more slowly rejected as unrelated than their control pairs, suggesting phonological access of word meanings. In Experiment 2, word-pseudohomophone pairs (e.g., TABLE-CHARE) and their visual controls (e.g., TABLE-CHARK) as well as related and unrelated word pairs were presented. Pseudohomophone pairs were more likely to be judged as related or more slowly rejected as unrelated than their control pairs, again suggesting automatic phonological recording in reading.

Adult↗

Comparison of isoflurane with sevoflurane for anesthesia induction and recovery in adult dogs.

OBJECTIVE: To compare mask anesthesia induction and recovery characteristics between 2 inhalant anesthetic agents: isoflurane and sevoflurane. ANIMALS: 16 clinically normal, young adult Beagles. PROCEDURE: Using a cross-over design, dogs were randomly selected to receive sevoflurane or isoflurane via a face mask and a circle anesthetic system. Vaporizer setting concentrations were increased in stepwise, equal minimum alveolar concentrations (MAC) for each anesthetic until the vaporizer setting of 2.6% for isoflurane or 4.8% for sevoflurane (2 MAC) was reached. Concentration was kept constant until the dog had a negative tail clamp response and was intubated. End-tidal concentration was maintained at 1.8 to 2.0% or 3.3 to 3.8% for isoflurane or sevoflurane, respectively (1.4 to 1.6 MAC) for 30 minutes. Dogs were allowed to recover with only tail clamp stimulation until a positive response was obtained. Extubation was performed when a spontaneous swallow reflex was observed. Dogs were allowed to achieve sternal recumbency and stand unassisted without further stimulation. RESULTS: Sevoflurane induction resulted in shorter time to loss of palpebral reflex, negative tail clamp response, and time to tracheal intubation, and was of better quality than isoflurane induction. Both anesthetics were associated with rapid and smooth recovery. CONCLUSIONS: Sevoflurane mask induction is faster and of better quality, compared with isoflurane, in adult dogs. Recovery time and quality are comparable. CLINICAL RELEVANCE: On the basis of these results, sevoflurane is a suitable inhalant anesthetic for mask induction and recovery in adult dogs and appears to have some advantages over isoflurane, including faster and smoother mask induction.

Analysis of Variance↗

Latex allergy.

An overview of latex allergy, including methods for preventing reactions and reducing exposure to latex, is provided. Latex allergy is a serious medical problem for an increasing number of patients and health care workers. From an institutional perspective, several precautionary procedures need to be followed to ensure safe care for patients and to protect employees from unnecessary latex exposure. These include establishing a multidisciplinary committee to develop policies and procedures; identifying products containing latex; identifying latex-sensitive patients and employees as well as those at high risk of developing the sensitivity; implementing precautions against allergic reactions to latex; educating personnel and patients on latex allergy; and reviewing quality assurance data to continually improve precautionary procedures. Pharmacists should be involved in developing and implementing these procedures. In particular, they can play a major role in the education of health professionals and patients. There is a strong need for more information on latex sensitivity, especially in the areas of epidemiology, product development, and effectiveness of procedures. Each institution, including its pharmacists, must evaluate the available information about latex sensitivity and determine appropriate actions.

Allergens↗

Role of carbon monoxide in heme-induced vasodilation.

We investigated the effects of carbon monoxide and heme-L-lysinate on the diameter of isolated, pressurized gracilis muscle arterioles. Both agents increased arteriolar diameter. The vasodilatory effect of heme-L-lysinate, but not of carbon monoxide was prevented by an inhibitor of heme oxygenase. Hence, heme-L-lysinate-induced vasodilation appears to be mediated by a product of vascular heme metabolism, presumably carbon monoxide. This implies that vascular formation of carbon monoxide may subserve a vasodilatory function.

Animals↗

Isozyme-dependent sensitivity of adenylyl cyclases to P-site-mediated inhibition by adenine nucleosides and nucleoside 3'-polyphosphates.

Recombinant adenylyl cyclase isozyme Types I, II, VI, VII, and three splice variants of Type VIII were compared for their sensitivity to P-site-mediated inhibition by several adenine nucleoside derivatives and by the family of recently synthesized adenine nucleoside 3'-polyphosphates (Désaubry, L., Shoshani, I., and Johnson, R. A. (1996) J. Biol. Chem. 271, 14028-14034). Inhibitory potencies were dependent on isozyme type, the mode of activation of the respective isozymes, and on P-site ligand. For the nucleoside derivatives potency typically followed the order 2',5'-dideoxyadenosine (2',5'-ddAdo) > beta-adenosine > 9-(cyclopentyl)-adenine (9-CP-Ade) >/= 9-(tetrahydrofuryl)-adenine (9-THF-Ade; SQ 22,536), with the exception of Type II adenylyl cyclase, which was essentially insensitive to inhibition by 9-CP-Ade. For the adenine nucleoside 3'-polyphosphates inhibitory potency followed the order Ado < 2'-dAdo < 2',5'-ddAdo and 3'-mono- < 3'-di- < 3'-triphosphate. Differences in potency of these ligands were noted between isozymes. The most potent ligand was 2',5'-dd-3'-ATP with IC50 values of 40-300 nM. The data demonstrate isozyme selectivity for some ligands, suggesting the possibility of isozyme-selective inhibitors to take advantage of differences in P-site domains among adenylyl cyclase isozymes. Differential expression of adenylyl cyclase isozymes may dictate the physiological sensitivity and hence importance of this regulatory mechanism in different cells or tissues.

Adenosine↗

Chronic varicella zoster infection mimicking a basal cell carcinoma in an AIDS patient.

Chronic herpesvirus infections are common in patients infected with HIV. Atypical skin lesions secondary to long-standing varicella-zoster virus (VZV) infection have been reported. We present a case of an AIDS patient with a chronic VZV infection that simulated a basal cell carcinoma. Histologic examination and immunohistochemistry confirmed the presence of the virus in the follicular epithelium. In the immunocompromised patient, biopsies should be performed on all suspicious lesions because medically-treatable infections may take on the appearance of malignancy.

AIDS-Related Opportunistic Infections↗

Residential preferences and eldercare views of Hispanic elders.

A cross-sectional, qualitative study was undertaken with a group (n = 10) of elderly Mexican-American men and women in an inner city congregate meal site of a large Midwestern city. The purpose of the study was to explicate: the older adults' residential preferences should they become unable to live in their own homes, and their beliefs about eldercare. Themes arising from the semi-structured interviews include: nursing homes as places of last resort, the desire not to be a burden to children, intergenerational differences in lifestyle, and extended family involvement in eldercare. Implications of the findings for helping professionals are discussed as are areas needing further investigation.

Journal Article↗

Role of endogenous carbon monoxide in central regulation of arterial pressure.

We investigated the contribution of neural mechanisms to the arterial pressure increase produced by zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG), an inhibitor of endogenous carbon monoxide synthesis. The arterial baroreceptor reflex control of heart rate was examined in rats with and without ZnDPBG pretreatment (45 micromol/kg IP) by analysis of the arterial pressure-heart rate relationship during infusions of phenylephrine or sodium nitroprusside to vary arterial pressure. ZnDPBG increased arterial pressure from 110 +/- 3 to 126 +/- 2 mm Hg without eliciting bradycardia. The maximum gain of the heart rate response to changes in arterial pressure was attenuated by ZnDPBG treatment (-1.9 +/- 0.3 versus -4.8 +/- 1.0 bpm/mm Hg). The possibility that ZnDPBG elevates arterial pressure by attenuating baroreceptor reflex function was addressed by comparing the pressor response to ZnDPBG (45 micromol/kg IP) in rats with and without sinoaortic denervation. The pressor effect of ZnDPBG was similar in rats with and without arterial baroreceptor deafferentation, implying that the increase in pressure is not simply the consequence of attenuated baroreceptor reflex function per se. The possibility that ZnDPBG increases arterial pressure via an effect on the nucleus tractus solitarii (NTS) also was investigated. ZnDPBG (1 nmol in 100 nL) injected into the NTS of rats increased arterial pressure from 111 +/- 4 to 126 +/- 5 mm Hg, and this effect was reversed by an ipsilateral microinjection of carbon monoxide into the NTS. Accordingly, the pressor effect of ZnDPBG may rely on inhibition of carbon monoxide production in the NTS. This implies that carbon monoxide formed by brain heme oxygenase plays a role in the central regulation of arterial pressure.

Animals↗

Inhibition of adenylyl cyclase by a family of newly synthesized adenine nucleoside 3'-polyphosphates.

The synthesis of a number of adenine nucleoside 3'-polyphosphates has been devised via a phosphotriester approach that combines the method of alkoxide activation with the use of 2,2,2-tribromoethyl phosphoromorpholinochloridate as a phosphorylating agent. The family of compounds included 3'ADP, 3'ATP, 2'-deoxy-3'ADP, 2'-deoxy-3'ATP, 2',5'-dideoxy-3'ADP, and 2',5'-dideoxy-3'ATP. Potency as inhibitors of adenylyl cyclases followed the order: 3'-mono- < 3'-di- < 3'-triphosphate and adenosine (Ado) < 2'-d-Ado < 2',5'-dd-Ado derivatives, with 2',5'-dideoxy-3'ATP exhibiting an IC50 of approximately 40 nM. This order was maintained with purified and recombinant forms of the type I enzyme. The nucleoside 3'-phosphates caused noncompetitive inhibition of the type I adenylyl cyclase from bovine brain, consistent with inhibition via the P-site. Inhibition was not due to hydrolytic products because this was minimal and inhibition kinetics by inorganic polyphosphates were inconsistent with those caused by the nucleoside 3'-polyphosphates. Only 3'ATP underwent cation-catalyzed, nonenzymatic hydrolysis, with the primary product being 2':3'-cAMP. Because 3'-ADP and 3'-ATP are naturally occurring, this class of compounds may physiologically regulate adenylyl cyclases and possibly other enzymes, mediating responses that include a reduction in 3':5'-cAMP levels and consequent reductions in protein kinase A-activated pathways.

Adenine Nucleotides↗

2',5'-Dideoxyadenosine 3'-polyphosphates are potent inhibitors of adenylyl cyclases.

2',5'-Dideoxyadenosine 3'-di- and triphosphates were tested as inhibitors of brain adenylyl cyclases. With an IC50 approximately 40 nM, 2',5'-dideoxy-3'-ATP is the most potent nonprotein synthetic regulator of adenylyl cyclases thus far described. Neither 2',5'-dideoxy-3'-ADP nor 2',5'-dideoxy-3'-ATP inhibited activity by competition with substrate, and the linear noncompetitive inhibition observed was consistent with interaction via a distinct domain. The availability of this ligand will permit the development of a variety of probes that will be extremely useful in investigating adenylyl cyclase structure and the role(s) that this class of compound may play in physiologically regulating cell function.

Adenylyl Cyclase Inhibitors↗

Heme oxygenase substrates acutely lower blood pressure in hypertensive rats.

Heme oxygenase catalyzes the metabolism of heme to biliverdine, free iron, and carbon monoxide. The current study was designed to determine if treatment with the heme oxygenase substrates heme-L-arginate or heme-L-lysinate, to stimulate formation of heme oxygenase products, can lower blood pressure in the rat. Heme-L-arginate (45 mumol/kg ip) and heme-L-lysinate (45 mumol/kg ip) acutely lowered blood pressure in awake spontaneously hypertensive rats (SHR) by approximately 35 mmHg. For both heme oxygenase substrates, this effect was blunted by pretreatment with an inhibitor of heme oxygenase, zinc deuteroporphyrin 2,4-bis glycol. Heme-L-lysinate also lowered arterial pressure in deoxycorticosterone acetate-salt hypertensive rats and in rats with phenylephrine-induced hypertension, indicating that the vasodepressive actions of heme may be extended to other hypertensive models. However, neither heme-L-arginate nor heme-L-lysinate decreased blood pressure in normotensive controls. The heme oxygenase product biliverdine did not lower blood pressure in SHR, and the vasodepressive actions of heme-L-lysinate were unaffected by pretreatment with deferoxamine to chelate free iron. Carbon monoxide (12 ml/kg ip) lowered blood pressure in SHR and in rats made hypertensive by phenylephrine infusion, had no effect on blood pressure in Wistar-Kyoto rats, and elicited only a modest vasodepressive response in normotensive Sprague-Dawley rats. We conclude that heme-bearing preparations can lower blood pressure in hypertensive rats, presumably via heme oxygenase-mediated formation of carbon monoxide.

Animals↗

The meaning of relocation among elderly religious sisters.

The meaning of involuntary, intra-institutional relocation (a move in primary living space) was constructed in this qualitative study through semistructured interviews with 12 elderly religious sisters. A thematic analysis of the data elicited from audiotape-recorded interviews was conducted. Overall, themes emerging from the sisters' discussion of the relocation included relocation as preparation for the future (to ensure their care in advancing years) and possibilities and consequences (resulting in improved living conditions together with sacrifice, uprooting, isolation, and distancing). Although relocation was seen as a largely positive event, it also had negative meaning for the subjects.

Adaptation, Psychological↗

Structural determinants of putrescine uptake inhibition produced by cationic diamidines in the model of trypanosomatid Crithidia fasciculata.

The effect of a heterologous series of cationic diamidines has been tested on cell growth and polyamine uptake on the model of insect Trypanosomatid Crithidia fasciculata. The maximum inhibitory effect on both parameters was found for pentamidine and dibromopropamidine, which exhibit a longer distance between amino and imino substituents. A minimum inhibitory effect was found with amicarbalide. A good relationship was obtained when the distance between amino moieties was plotted versus the inhibitory effect on putrescine uptake, suggesting a role of this structural property on polyamine transport in Crithidia fasciculata. In addition, a similar correlation was obtained for another Trypanosomatid parasite, Leishmania infantum.

Animals↗

Effect of ifetroban, a thromboxane A2 receptor antagonist, in stroke-prone spontaneously hypertensive rats.

Experiments were performed to determine the effect of chronic therapy with the potent and long-acting thromboxane (TX) A2/prostaglandin endoperoxide (TP) receptor antagonist, ifetroban, on hypertension development and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP instrumented with radiotelemetry probes, for continuous monitoring of arterial blood pressure, were given 1% NaCl to drink and Stroke-Prone Rodent Diet and were chronically treated with ifetroban (20 mg/kg/day, n = 10) or vehicle (n = 12) starting at 16.5 weeks of age. Ifetroban did not affect blood pressure or the development of proteinuria and cerebrovascular lesions. Chronic administration of a higher dose ifetroban (40 mg/kg/day) starting at 7 weeks of age was also without effect on blood pressure and stroke in noninstrumented saline-drinking SHRSP. These results do not support a major role for TXA2 and its endoperoxide precursors in the elevation of blood pressure and the development of cerebrovascular lesions in saline-drinking SHRSP.

Animals↗

Microbiological N-deoxygenation and C-oxygenation of pioglitazone-N-oxide in a single fermentation.

Oxygenation of pioglitazone-N-oxide by a microorganism isolated from soil was accompanied by N-deoxygenation to produce the pioglitazone metabolites 5-[4-[2-[5-(1-hydroxyethyl)-2-pyridyl]ethoxy]benzyl]-2,4-thiazolidinedio ne and 5-[4-[2-(5-acetyl-2-pyridyl)ethoxy]benzyl]2,4-thiazolidinedione. The oxygenating/deoxygenating organism has been characterized as Streptomyces hygroscopicus strain 02179 (UC 11099). The culture has been deposited with Agricultural Research Service, USDA, with accession number NRRL 18975.

Fermentation↗

Azido-iodo-phenyl-analogs of 2',5'-dideoxy-adenosine as photoaffinity ligands for adenylyl cyclase.

Azidoiodophenyl-analogs of 2',5'-dideoxyadenosine were synthesized and tested as potential 'P'-site selective affinity probes for adenylyl cyclases. The 3'-substituted analogs included: 1: 3'-[(4-nitrophenyl)-acetyl]-2',5'-dideoxy-adenosine 2: 3'-[(4-nitrophenyl)-butyryl]-2',5'-dideoxyadenosine 3: 3'-[(4-azido-3-iodophenyl)-acetyl]-2',5'-dideoxyadenosine and 4: 3'-[(4-azido-3-iodophenyl)-butyryl]-2',5'-dideoxyadenosine. The azidoiodo-phenyl-analogs inactivated adenylyl cyclase irreversibly and in a light-dependent manner. This was observed with detergent-dispersed enzyme from rat brain, purified native enzyme from bovine brain, and recombinant Type I bovine adenylyl cyclase expressed in membranes from fall army worm ovarian (Sf9) cells. Inactivation of the recombinant enzyme was inversely dependent on ATP concentration and was not completely prevented by 2',5'-dideoxyadenosine. Inhibition kinetics with the recombinant enzyme in the absence of light suggested two sites of inhibition, whereas with the native Type I enzyme inhibition kinetics exhibited a straightforward noncompetitive mechanism. Occupation of either or both sites by ligand protected the enzyme against denaturation by UV-irradiation per se. The data are consistent with inactivation of the recombinant enzyme occurring both through the 'P'-site and the catalytic active site, but suggest that this is a characteristic of the recombinant enzyme and is not dependent on the probes per se. The data suggest the potential for independent interactions of such ligands with different sites on a given enzyme and also with other enzymes containing adenosine or adenine nucleotide binding domains.

Adenosine Triphosphate↗