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Biomedical subjects

E Johnson

Publications and source records attributed to E Johnson.

At least 415 records · Page 23Linked to original sources
PubMedDate not supplied

The role of stress in the regulation of drug metabolizing enzymes in mice.

The role of stress in the regulation of several enzymatic systems which are involved in the biotransformation of xenobiotics in the liver was investigated in this study using restraint stress as a stress model. The results demonstrated that stress suppressed total basal P450 content (35%) and basal ethoxyresorufin 7-dealkylase (EROD) activity (33%), while slightly increasing basal methoxyresorufin 7-dealkylase (MROD) activity (20%). Basal pentoxyresorufin 7- dealkylase (PROD) and coumarin 7-hydroxylase (COH) activities were not affected. On the other hand, restraint stress increased total P450 content in 1,4-bis[2-(3,5- dichloropyridyloxy)]benzene (TCPOBOP)-treated mice (35%), while slightly suppressing PROD activity (26%). In addition, CYP2E1 dependent p-nitrophenol hydroxylation (PNP), was suppressed (40%) by stress in TCPOBOP-treated animals and cytosolic aldehyde dehydrogenases were not affected. Although stress had no effect on basal P4502A5 activity, the inducibility of this hepatic activity increased 2-fold after stress exposure. A pronounced suppression (7-fold) in glutathione content was observed in lungs of TCPOBOP treated mice after stress, whereas basal levels remained unaffected. In addition, only a slight suppression (20%) in liver glutathione content was found in both treatment groups. Northern blot analysis revealed that restraint stress had a relatively suppressive effect on control CYP1A2 expression in the liver. In contrast, stress markedly enhanced the expression of liver CYP2A5 in TCPOBOP-treated mice, but did so to a lesser extent in controls. Stress also increased CYP2A5 mRNA in TCPOBOP-treated mice to a greater degree than the activity of the corresponding cytochrome. On the other hand, liver P4502A5 activity was found to be induced by TCPOBOP by about 2.5-fold. However, the drug does not appear to be involved in the expression of CYP2A5. Finally, although the activity of liver P4502A5 cytochrome was found to be increased 3, 8 and 27 h after stress, after which it gradually declined up to 75 h, CYP2A5 liver expression appeared to be suppressed 3, 8, 27 and 51 h after stress, while 75 h later it apparently reached normal levels. In conclusion, the results of this study showed that restraint stress significantly alters several enzymatic systems differently at a basal level than under conditions of TCPOBOP induction. In addition, stress was found to significantly interfere with the expression processes of CYP1A2 and CYP2A5.

Aldehyde Dehydrogenase↗
PubMedDate not supplied

Evidence of alpha2-adrenoceptor involvement in B[alpha]P induction processes of drug-metabolizing enzymes: the effect of stress.

Central to the appropriate regulation of behavioral and physiological changes induced by stress are the noradrenergic neuronal systems which have been implicated in a large number of stress-induced pathophysiological states. Endoplasmic reticulum-bound cytochromes (CYPs) play a crucial role in drug metabolism, resulting in deactivation or formation of reactive derivatives. In turn, these products may be responsible for the chemotherapeutic, mutagenic or carcinogenic properties of the parent compound. The present study assesses the effect of a specific alpha2- adrenoceptor agonist, dexmedetomidine (DEXT), on stress-induced modification of cytochrome activity in rats using a restraint stress model. The results indicated that activation of the alpha2-adrenoceptor with DEXT did not alter basal hepatic methoxyresorufin 7-dealkylase (MROD). On the other hand, it appeared to enhance MROD in benzo[alpha]pyrene (B[alpha]P) treated animals. Of interest was the finding that stress blocked DEXT-induced MROD enhancement in B[alpha]P- treated rats. In addition, DEXT had no effect on basal hepatic pentoxyresorufin 7-dealkylase (PROD), while it further enhanced the strong induction by B[alpha]P. Stress was also found to block this effect. Hepatic ethoxyresorufin 7-dealkylase (EROD) activity was strongly increased by B[alpha]P; this effect was enhanced by DEXT. In contrast, the DEXT enhanced induction was further strengthened by stress. These findings suggest that alpha2-adrenoceptors may modulate the induction of cytochromes CYP1A1, 1A2 and 2B1 by B[alpha]P in rats and that stress may modify this process. In particular, stress may regulate the inducibility of P4501A1 activity by B[alpha]P via mechanisms related to alpha2-adrenoceptors.

Adrenergic alpha-2 Receptor Agonists↗
PubMedDate not supplied

Transmission of Ebola virus (Zaire strain) to uninfected control monkeys in a biocontainment laboratory.

Secondary transmission of Ebola virus infection in humans is known to be caused by direct contact with infected patients or body fluids. We report transmission of Ebola virus (Zaire strain) to two of three control rhesus monkeys (Macaca mulatta) that did not have direct contact with experimentally inoculated monkeys held in the same room. The two control monkeys died from Ebola virus infections at 10 and 11 days after the last experimentally inoculated monkey had died. The most likely route of infection of the control monkeys was aerosol, oral or conjunctival exposure to virus-laden droplets secreted or excreted from the experimentally inoculated monkeys. These observations suggest approaches to the study of routes of transmission to and among humans.

Aerosols↗
PubMedDate not supplied

Bacteriologic studies on electronic hospital thermometers.

Electronic thermometers used in many hospitals require insertion into the mouth of a temperature-sensing probe covered by a pre-packaged probe cover. Handling procedures used by hospital personnel can lead to inadvertent manual contact with the probe cover. We attempted to determine the rate of non-sterility of these probe covers under normal hospital conditions and the extent to which pathogens could be detected on these and other components of the thermometer. Probe covers were removed before entry into the patient's mouth and aseptically inoculated into fluid thioglycollate medium. Subcultures were made to appropriate differential media. Over a 13-week period, 180 covers were cultured on two private hospital services. Forty-three percent were found to be non-sterile; control covers from central supply were only 6% non-sterile. Four percent of the probe covers harbored potential pathogens: coagulase positive Staphylococcus aureus, Streptococcus pyogenes, Enterobacter, and Bacteroides. No attempt was made to correlate these findings with infection. These results indicated a potential infection hazard for high-risk patient groups and a need by hospital personnel to consider this as a possible source of contamination.

Bacteria↗
PubMedDate not supplied

Studies on 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine, a nonneurotoxic analogue of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Previous reports indicate that 4-benzyl-1-methyl-1,2,3,6-tetrahydropyridine (BMTP), the benzyl analogue of the Parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is not neurotoxic in the C-57 black mouse even when administered at a dose 10 times greater than the dose of MPTP required to cause an 85% depletion of neostriatal dopamine. Intrastriatal microdialysis in the rat with the corresponding 4-benzyl-1-methylpyridinium ion BMP+ for 60 min, however, causes nerve terminal destruction similar to that observed following a 15-min perfusion with the 1-methyl-4-phenylpyridinium ion MPP+, the monoamine oxidase B (MAO-B) generated metabolite derived from MPTP. With the aid of purified beef liver MAO-B and synthetic standards, we observed the efficient and quantitative conversion of BMTP to the corresponding 2,3-dihydropyridinium intermediate BMDP+, which underwent further, but incomplete, oxidation to BMP+. These MPTP-type properties point to in vivo effects, such as pharmacokinetic parameters and/or alternative metabolic pathways, to account for BMTP's lack of neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Current distribution under electrodes in relation to stimulation current and skin blood flow: are modern electrodes really providing the current distribution during stimulation we believe they are?

Carbonized rubber electrodes were tested extensively when they were first developed 30 years ago, but modern carbonized rubber electrodes have not received the type of scrutiny that the first electrodes received. Modern electrodes differ from the original electrodes in that they come with a self-adhesive electrode gel called hydrogel as part of their composition. The present study was undertaken to examine the current distribution and impedance characteristics of five brands of carbonized rubber electrodes and to examine the current distribution between electrodes during electrical stimulation in six subjects. Several different electrode sizes were tested between 3 and 10 cm. The current flow between the electrodes was determined by measuring the voltage across the skin on human subjects in 15 discrete locations between the electrodes. Blood flow was also measured between the electrodes with a laser Doppler flow meter to assess the physiological effect of current distribution on the skin at several skin temperatures. The results of these studies showed that at low currents, such as is used in TENS, very little current is actually applied through the skin due to the high impedance of the electrodes. At current levels normally used for electrical stimulation for functional movement, while current flow is better in most electrodes, it is very uneven, resulting in high current density in the centre of the electrodes and a fall off of at least 50% in current intensity at the edges of the electrode. There was very little difference in current density between small and large electrodes due to the high current density in the centre. Skin blood flow altered the movement of current between the electrodes and also may contribute to electrode performance. The implication of these studies is that electrode design needs to be altered for better current distribution, especially at low stimulation currents.

Adult↗
PubMedDate not supplied

EMS-initiated refusal and alternative methods of transport.

OBJECTIVES: 1) To describe characteristics of patient transport protocols in those U.S. cities that sanction EMS-initiated refusal of transport; and 2) to describe the frequency and type of alternatives to emergency ambulance transport. METHODS: EMS systems in every one of the 200 largest cities in the United States were surveyed by telephone regarding EMS-initiated refusal policies, involvement of physicians in the decision-making process, and the presence or absence of alternatives to EMS transport. RESULTS: 100% of the target population responded to the telephone survey. Only 34 (17%) EMS systems have written protocols that allow EMS providers to refuse emergency ambulance transport for patients judged to have minor illness or injury after examination. Twenty-one (62%) of these EMS systems do not require on-line physician approval for EMS-initiated refusals. Seven (21%) EMS systems that allow refusal of transport also have a formalized alternative transport program in place. Nationwide, only 19 (10%) cities surveyed offer some type of alternative to ambulance transport, most commonly taxi and minivan. CONCLUSION: The authors report the first national survey of EMS-initiated refusal practices. Few urban EMS systems have implemented this policy to decrease utilization by persons with low-acuity illness or injury. This may be related to the fact that few EMS systems currently have alternatives to emergency ambulance transport.

Clinical Protocols↗
PubMedDate not supplied

Congenital dislocation of the knee.

Twenty-three congenital knee dislocations in 17 patients were reviewed after an average follow-up of 11 years. There was a 30% incidence of breech delivery along with a 41% incidence of clubfoot. Treatment in serial casts was successful in 10 knees; 13 required operations. Prognosis was most favorable in unilateral cases and when surgery was performed before 2 years of age. Quadriceps lengthening during knee surgery facilitated the subsequent reduction of ipsilateral dislocated hip.

Adolescent↗
PubMedDate not supplied

Cellular immune responses in rhesus macaques infected rectally with low dose simian immunodeficiency virus.

Monkeys infected rectally with low dose simian immunodeficiency virus (SIV) were resistant to high dose challenge with SIV. Peripheral blood mononuclear cells (PBMC) from two of four challenged monkeys were unable to support SIV replication in vitro unless cultures were depleted of CD8+ lymphocytes. Monkeys that had survived high dose rectal infection with SIV also suppressed virus replication in cultured PBMC. PBMC from uninfected monkeys supported virus replication in both unfractionated and CD8-depleted cultures. Virus-suppressive activity of PBMC may be an important correlate of protective immunity in AIDS.

Animals↗
PubMedDate not supplied

Vitronectin modulates the expression of complement components of the terminal pathway synthesized by human umbilical vein endothelial cells in vitro.

In this study we demonstrate that human endothelial cells (EC) synthesize mRNA for vitronectin by using techniques based on reverse transcriptase (RT) reaction and polymerase chain reaction (PCR). The identification of vitronectin mRNA, shown by sequence analysis of PCR-amplified RT product of RNA extracted from EC, clearly demonstrates that these cells synthesize mRNA for vitronection. We further investigated whether vitronectin in serum-free EC cultures regulates the net expression of the terminal complement pathway, measured as the terminal complement complex (TCC) bound to co-cultured agarose beads which activate the alternative pathway. Presence of polyclonal F(ab')2 anti-human vitronectin (VN) antibodies, regardless of concentration (10-80 micrograms/ml), significantly reduced the binding of monoclonal anti-C3c antibodies to co-cultured beads, whereas the binding of monoclonal anti-TCC antibodies was unaltered or significantly increased compared with controls. Despite some interexperimental variation in the results, addition of vitronectin (10-80 micrograms/ml) to the EC resulted in an inversely related pattern compared with experiments using anti-VN antibodies. The binding indices of anti-C3c are comparable to the controls. On the other hand, there is a steady concentration-dependent (10-80 micrograms of vitronectin added) reduction in binding of anti-TCC up to approximately 60%. The results indicate that vitronectin regulates the expression of synthezised and surface-bound TCC in serum-free EC cultures, comparable to previous findings in serum.

Cells, Cultured↗
PubMedDate not supplied

Preventing fungal infections in immunocompromised patients.

The incidence of systemic fungal infections in immunosuppressed patients has increased in the past two decades (Fridkin and Jarvis, 1996). Bone marrow transplant recipients and patients with prolonged neutropenia are most at risk, particularly when environmental factors increase the presence of fungi and fungal spores. Preventive measures include air filtration, handwashing, exclusion of flowers and some foodstuffs and use of chemoprophylaxis. In April 1999, a meeting was held under the auspices of the European Group for Blood and Marrow Transplantation (UK) Nurses and Allied Professionals Group to discuss the role of nurses in the management of patients at risk of systemic fungal infection. Issues discussed included: the need for nurses to recognize risk factors for systemic fungal infection; the role of nurses in giving feedback to patients; and the use of antifungal agents and associated problems, such as non-compliance and side-effects.

Bone Marrow Transplantation↗