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Biomedical subjects

M N Johnson

Publications and source records attributed to M N Johnson.

At least 19 recordsLinked to original sources
PubMed1998

Inhibition of antagonist and agonist binding to the human brain muscarinic receptor by arachidonic acid.

Arachidonic acid (AA) inhibits the binding of [3H]quinclidinyl benzilate ([3H]QNB) to the human brain muscarinic cholinergic receptor (mAChR). AA inhibits at lower concentrations in the absence of glutathione (I50 = 15 microM) than in the presence of glutathione (I50 = 42 microM). Inhibition of mAChR binding shows specificity for AA and is reduced with loss of one or more double bonds or with either a decrease or increase in the length of the fatty acid chain. Metabolism of AA by the lipoxygenase, epoxygenase, or fatty acid cyclooxygenase pathways is not required for the inhibitory activity of AA on mAChR binding. Inhibition of [3H]QNB binding by AA is reversible. While decreasing Bmax, AA increased the apparent KD for [3H]QNB and for the more polar antagonist [3H]NMS. In addition, AA inhibits binding of the agonist [3H]oxotremorine-M (I50 = 60 microM) and is the first mediator of mAChR action to be shown to reversibly inhibit mAChR binding. The feedback inhibition of the mAChR by AA may serve a homeostatic function similar to the reuptake and hydrolysis of acetylcholine following cholinergic nerve transmission.

Adult↗
PubMed1996

Endogenous Alzheimer's brain factor and oxidized glutathione inhibit antagonist binding to the muscarinic receptor.

An endogenous inhibitor (< 3,500 Da) of antagonist binding to the muscarinic acetylcholine receptor has been extracted from Alzheimer's disease (AD) brain with trifluoracetic acid. Oxidized glutathione, (GSSG) has also been found to inhibit antagonist binding to the receptor. However, in its reduced form, glutathione (GSH) like other reducing agents, markedly enhances the inhibitory effect of both GSSG and the endogenous AD inhibitor. EDTA and the free radical scavengers Mn(2+) and Trolox, a vitamin E analog, block the action of the endogenous AD inhibitor but not of GSSG in the presence of GSH. Further, while GSSG inhibition is reversible, the action of the endogenous AD inhibitor is irreversible, consistent with a free radical mechanism. The enhancement of endogenous AD inhibitor activity by GSH suggested that GSH may be involved in formation of the free radical generated by the inhibitor. The glutathione thiyl radical is shown to inhibit antagonist binding to the receptor and is, therefore, a good candidate for the free radical formed by the endogenous AD inhibitor. The ability of Trolox to block the reduction in muscarinic receptor binding caused by the endogenous AD inhibitor is encouraging and suggests that free radical scavengers, such as vitamin E, may have a potential therapeutic role in AD by protecting the integrity of the muscarinic receptor.

Alzheimer Disease↗
PubMed1990

Effect of cocaine on the coronary circulation and systemic hemodynamics in dogs.

This study investigated the effect of intravenous cocaine (0.5 to 2 mg/kg body weight) on the coronary circulation and systemic hemodynamics in closed chest sedated dogs. The role of alpha- and beta-adrenoceptor stimulation in mediating these effects was also investigated. Cocaine produced dose-dependent increases in mean arterial pressure and rate-pressure product. Although the lower doses of cocaine had no significant effect on the coronary circulation, the 2 mg/kg dose produced a 55 +/- 14% increase in coronary vascular resistance (p less than 0.05 versus baseline) and a 19 +/- 3% reduction in diameter of the left anterior descending coronary artery (p less than 0.05 versus baseline). Despite these potentially deleterious effects on the coronary circulation (occurring at a time of markedly increased myocardial oxygen demand), the electrocardiogram did not demonstrate ischemic changes and there was no myocardial lactate production. Cocaine-induced coronary vasoconstriction was abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, but not by pretreatment with the beta-adrenoceptor antagonist propranolol. The findings that cocaine did not change systemic vascular resistance in dogs without adrenergic blockade, reduced systemic vascular resistance in dogs after alpha-blockade (p less than 0.05) and increased systemic vascular resistance in dogs after beta-blockade (p = 0.06) suggest that epinephrine (rather than norepinephrine) is primarily responsible for the peripheral vascular actions of cocaine. Thus, in this canine preparation with normal coronary arteries, cocaine produced vasoconstriction of both epicardial and coronary resistance vessels that was not associated with evidence of myocardial ischemia. The pharmacologic mechanism for the effect of cocaine on the coronary circulation is alpha-adrenoceptor stimulation, whereas systemic hemodynamic effects are mediated by combined alpha- and beta-adrenoceptor stimulation.

Animals↗
PubMed1983

Role perception and role enactment of the nurse and their determinants in a teaching hospital in Nigeria.

This study was conducted to compare nurses' perception of their role with the perception which physicians and patients have of the role of nurses in a teaching hospital incorporating a school of nursing and midwifery; to explore the underlying reasons for the discrepancies found; to examine the effects of discrepancies in role perception on the effectiveness of patient care and to discuss the findings in the light of nursing education curricula in Nigeria. Questionnaires, listing ten technical/instrumental and expressive/humanitarian nursing functions were administered to three groups of respondents (nurses, physicians and patients). They were requested to select any five statements that best described what nurses did, and to rank them according to how often the functions described were seen being practised. A second questionnaire, administered only to the nurse respondents, elicited a number of background parameters related to nursing career. The results from the first questionnaire show that nurses did not seem to agree with patients and physicians on the perception and enactment of their role. Nurses saw their role as equally technical/instrumental and expressive/humanitarian, whereas patients and physicians saw it as more expressive/humanitarian, the patients being particularly more inclined to this perception. Most significant was the disagreement between patients and nurses. Nurses whose perception of their role agreed most closely with that of physicians and patients, were found to be older, and to have had longer experience. A significant proportion of them had only basic nursing qualifications, and they perceived their functions to be more appreciated by patients.

Adult↗
PubMed1981

ICP changes following application of the MAST suit.

The MAST suit is used primarily in the field to raise arterial pressure in patients with hemorrhagic shock. By 'squeezing' blood back to the heart and compressing arteries, the suit acts to transfuse the patient as well as to compress bleeding sites. Because of the sudden increase in venous return with abdominal compression, its use has been questioned after closed head injury, cardiac tamponade, and/or tension pneumothorax. A study was devised to evaluate the MAST suit in dogs following hemorrhage and hemorrhage with the creation of a tension pneumothorax, cardiac tamponade, and mass intracranial lesion. Pulmonary artery, central venous, systemic arterial, and intracranial pressures were monitored in control dogs before and after hemorrhage and application of the MAST suit. Following hemorrhage, the inflated MAST suit raised systolic arterial pressure as well as central venous, pulmonary artery, and intracranial pressures. The rise in intracranial pressure mirrored the rise in venous pressure and never reached potentially harmful levels in the hemorrhaged animals and animals with a mass intracranial lesion. In the animals with cardiac tamponade and tension pneumothorax, inflation of the abdominal portion of the MAST suit produced a marked rise in central venous and intracranial pressures. This was altered by either relieving the lesion or reducing the pressure of the abdominal portion of the MAST suit.

Animals↗
PubMed1976

Capillary abnormalities in polyvinyl chloride production workers. Examination by in vivo microscopy.

Examination by wide-field capillary microscopy of the hands of 152 workers in vinyl chloride (VC) polymerization plants demonstrated scattered, scleroderma-like microvascular abnormalities in 21 workers and isolated capillary abnormalities in 27, as compared with only three isolated abnormalities in 50 manual workers not exposed to vinyl chloride. Thirteen of 17 VC workers with objective evidence of VC-associated abnormalities (angiosarcoma or fibrosis of liver, acroosteolysis, or scleroderma-like skin lesions) were observed to have microvascular abnormalities. If prospective studies confirm the implications of this study, capillary microscopy may become a useful mass-screening procedure in the early detection and prevention of VC-associated disease.

Adult↗
PubMed1976

Clinical and morphologic features of hepatic angiosarcoma in vinyl chloride workers.

Fifteen male workers exposed to vinyl chloride developed angiosarcoma of the liver. Thirteen died of disease and two are currently living for short periods after diagnosis. Their ages ranged from 36 to 58 years (average 47.5 years). Their exposure time ranged from 4 to 27.8 years (average 16.9 years). The most common presenting symptoms were fatigue, weight loss, and abdominal pain. Hepatomegaly followed by splenomegaly were the most common physical findings. Biochemical profiles yielded variable results and proved to be of little value in the detection or diagnosis. Of eight patients autopsied, distant organ involvement was present in two cases, duodenal involvement in one, and direct extension of tumor to adjacent organs or tissues in four additional ones. The remainder, diagnosed by open liver biopsy, revealed no tumor extension. The gross features of the tumors were hemorrhagic necrosis, cystic degeneration, fibrosis, and apparent multicentricity. The histologic features were those of the typical angiosarcoma found in a variety of sites with a wide range of cellular differentiation. The histologic diagnosis was often impaired by the extensive tumor necrosis. Elsewhere in the liver subcapsular fibrosis, a distinct type of portal fibrosis, and endothelial cell hyperplasia with or without sinusoidal dilatation were noted. The reduction of industrial chemical exposure has already been achieved and will hopefully eliminate this chemically related tumor in the future. There is, however, a significant group of previously exposed workers who will require careful monitoring to detect functional abnormalities of the liver and possible early neoplastic changes.

Adult↗