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Biomedical subjects

M J Robertson

Publications and source records attributed to M J Robertson.

At least 91 records · Page 5Linked to original sources
PubMed1992

Expression of sialyl-Lewis X, an E-selectin ligand, in inflammation, immune processes, and lymphoid tissues.

The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined.

Carbohydrate Metabolism↗
PubMed1991

Homeless women with children. The role of alcohol and other drug abuse.

For some women with children, alcohol and other drug use may be an important risk factor for homelessness because it may interfere with a woman's capacity to compete for scarce resources such as housing, employment, or services. The impact of various policy decisions on homeless women, their dependent children, and the family unit is considered, including women's right to privacy, criminalization of drug use, and scarcity of appropriate treatment programs for homeless women.

Adult↗
PubMed1991

Do renal tubular dopamine receptors mediate dopamine-induced diuresis in the anesthetized cat?

The aim of this study was to investigate whether the pentobarbitone anesthetized cat is a suitable preparation in which to characterize renal tubular dopamine receptors. Intravenous infusion of dopamine (10-100 micrograms/kg/min) resulted in a dose-related increase in mean blood pressure (MBP), urine output, sodium excretion (UNaV), and fractional sodium excretion (FENa). This diuretic effect occurred despite little change in glomerular filtration rate, suggesting that it is a consequence of decreased tubular reabsorption. Dopamine (10-100 micrograms/kg/min, i.v.) also induced marked dose-related falls in renal vascular conductance; however, renal blood flow was not significantly reduced. The increases in MBP, urine output, UNaV, and FENa induced by dopamine (10-100 micrograms/kg/min, i.v.), were unaffected by pretreatment of cats with either the selective dopamine DA1 or DA2 receptor antagonists, SCH 23390 (30 micrograms/kg, i.v.), or domperidone (100 micrograms/kg, i.v.) respectively. In contrast, pretreatment of cats with the nonselective alpha-adrenoceptor antagonist, phentolamine (1 mg/kg, i.v.) prevented dopamine-induced increases in urine output and MBP. Infusion of the selective dopamine DA1 receptor agonist fenoldopam (0.01-10 micrograms/kg/min) into the left renal artery failed to increase left renal vascular conductance, or left kidney urine output, UNaV, or FENa. In conclusion, this study provides no evidence for the involvement of renal tubular dopamine receptors in dopamine-induced diuresis in anesthetized cats. Rather, the diuretic effect appears to be linked to stimulation of alpha-adrenoceptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Effects of dopamine DA1-receptor blockade and angiotensin converting enzyme inhibition on the renal actions of fenoldopam in the anaesthetized dog.

Experiments were performed in anaesthetized dogs to characterize the renal effects of the selective dopamine DA1-receptor agonist, fenoldopam. Intrarenal artery infusion of fenoldopam (0.01-10 micrograms/kg per min) caused dose-related renal vasodilation. At low doses (0.01-0.3 micrograms/kg per min), renal vasodilation occurred without concomitant falls in blood pressure but was accompanied by increased urine output. This diuresis was most probably a result of reduced tubular reabsorption since glomerular filtration rate was not increased. Both fenoldopam-induced renal vasodilation and diuresis were blocked to a similar extent by the selective dopamine DA1-receptor antagonist, SCH 23390 (30 micrograms/kg, intravenously), suggesting that both effects were mediated by dopamine DA1-receptors. In the presence of the angiotensin converting enzyme inhibitor, captopril (1 mg/kg, intravenously, + 20 micrograms/kg per min, intrarenal artery), fenoldopam (0.01-0.3 micrograms/kg per min) significantly increased fractional excretion of sodium, despite reducing blood pressure; neither of these effects were observed in captopril-free dogs. These observations support the view that the inhibitory effect of fenoldopam on tubular function, and its vasodepressor activity, may be opposed by angiotensin II resulting from fenoldopam-induced renin release.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Successful treatment of disseminated Fusarium infection after autologous bone marrow transplantation for acute myeloid leukemia.

Disseminated Fusarium is a rare but life-threatening infection of severely immunocompromised patients. A fatal outcome has been described in all reported cases of Fusarium infection occurring after bone marrow transplantation. We describe a patient who developed disseminated Fusarium infection with a secondary fungal endophthalmitis after an autologous bone marrow transplant for acute myeloid leukemia. This infection was successfully eradicated after neutrophil recovery by prolonged systemic administration of amphotericin B as well as aggressive local therapy including enucleation of the affected eye. The patient remains free of both leukemia and fungal disease more than 4 years after transplant.

Adult↗
PubMed1990

Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis.

Cell adhesion molecules (CAM) participate in interactions between lymphocytes, accessory cells, and target cells that are critical in the generation of effective immune responses. To characterize the involvement of CAM in NK and lymphokine activated killer (LAK) activities, we examined the expression of several CAM by freshly isolated human NK cells and by NK cells activated in vitro with IL-2, and compared this to CAM expression by T lymphocytes under similar conditions. Freshly isolated human NK cells were uniformly LFA-3 (CD58)+ and expressed two to three-fold higher surface levels of LFA-1 (CD11a/CD18) than resting T lymphocytes. More NK cells than T cells also expressed phenotypically detectable levels of intercellular adhesion molecule-1 (CD54). After in vitro incubation with IL-2, human NK cells demonstrated four- to sixfold increases in surface levels of CD11a/CD18, CD2, CD54, CD58, and the NK cell-associated Ag NKH-1 (CD56). Furthermore, essentially all NK cells became CD54+ within 3 days of exposure to IL-2. T cells did not demonstrate comparable up-regulation of CAM after incubation with IL-2. Increases in NK cell CAM expression were associated with enhanced formation of E:T cell conjugates, enhanced killing of NK-sensitive targets, and the induction of cytotoxicity for previously NK-resistant targets (LAK activity). The LAK activity induced by exogenous IL-2 could be partially inhibited by anti-CD2, anti-CD11a, or anti-CD54 antibodies and almost completely abrogated by anti-CD2 and anti-CD11a in combination. These studies suggest that CAM play a central role in the regulation of NK cytolysis, and that changes in CAM expression may alter the target cell specificity of activated NK effectors.

Antibodies, Monoclonal↗
PubMed1989

Effects of hypoxia, elevated K+ and acidosis on the potency of verapamil, diltiazem and nifedipine in the guinea-pig isolated papillary muscle.

1 The effects of the structurally diverse calcium channel blockers verapamil, nifedipine and diltiazem were investigated on the force of contraction of guinea-pig, electrically stimulated papillary muscles in vitro. 2 Calcium channel blocking potency was assessed either as a direct negative inotropic effect or as the ability of the drugs to antagonise the positive inotropic effects of added calcium (Ca2+). By either method, the rank order of potency was found to be nifedipine greater than verapamil greater than diltiazem. 3 Various factors which mimic some of the consequences of acute ischaemia in vivo, namely low pH, hypoxia and elevated K+, in combination, but not singly, enhanced the negative inotropic potency of verapamil and to lesser extent that of diltiazem, but not that of nifedipine. 4 Whilst the various interventions, especially in combination, produced a profound negative inotropic effect themselves, this was not responsible per se for the potentiation of the negative inotropic effects of verapamil and diltiazem, since the negative inotropic effects of nifedipine and dinitrophenol were not potentiated under the 'ischaemic' conditions. 5 By use of antagonism of the positive inotropic action of exogenous Ca2+ as an alternative measure of potency, the differential influence of 'ischaemia' on calcium channel blocker potency was confirmed. The effect of verapamil was potentiated some 9 fold, that of diltiazem about 2 fold, and that of nifedipine was unchanged. 6 The differential effect of 'ischaemia' on the potencies of the calcium channel blockers was unexpected. Verapamil (but not nifedipine) is thought to bind to the calcium channel at a specific site not easily accessible from the extracellular space. 'Ischaemic' conditions may cause membranal perturbations which allow verapamil easier access to its binding site thus increasing its negative inotropic potency.

Acidosis↗
PubMed1988

Recurrent fungal pneumonias in patients with acute nonlymphocytic leukemia undergoing multiple courses of intensive chemotherapy.

The records of 40 consecutive patients with newly diagnosed acute nonlymphocytic leukemia (ANLL) were reviewed to determine the risk of recurrent fungal pneumonia during multiple episodes of chemotherapy-induced granulocytopenia. Fungal pneumonias were diagnosed as proven or probable using defined pathologic, microbiologic, radiologic, and clinical criteria. Sixteen patients died without a complete remission; of these, all 11 who underwent autopsy were found to have invasive fungal pneumonia. The 24 patients who achieved a complete remission received one to nine (median, four) additional courses of intensive chemotherapy for remission consolidation and/or relapse, and experienced 132 episodes of severe granulocytopenia. Seven patients never had a pulmonary infection despite 34 granulocytopenic episodes. However, fungal pneumonia complicated 32 (33 percent) of 98 granulocytopenic episodes in the other 17 patients. Fifteen of the patients who achieved a complete remission had at least one episode of fungal pneumonia; 12 received further chemotherapy, and nine (75 percent) of these had a subsequent fungal pneumonia. In all, 17 (52 percent) of 33 subsequent granulocytopenic episodes experienced by patients with a prior fungal pneumonia were complicated by another fungal pneumonia. All four patients with a probable fungal pneumonia diagnosed antemortem who subsequently underwent autopsy were found to have invasive fungal disease. It would appear that patients with ANLL who have had one episode of fungal pneumonia are at high risk for recurrence during subsequent episodes of granulocytopenia. Empiric or even prophylactic amphotericin B therapy may be warranted for such patients.

Acute Disease↗
PubMed1986

Health status and access to health services among the urban homeless.

Self-reported health status and access to care were reported for 238 homeless adults in Los Angeles. One-third reported their health as fair or poor; women reported more health problems than men. Half (53 per cent) of the sample reported no regular source of care, and most (81 per cent) were without health insurance. Lack of financial resources and health insurance were reported as important barriers to care.

Adult↗
PubMed1983

Chronic opiate treatment does not modify alpha 2-adrenergic receptors in rat cerebral cortex, kidney and in the neurotumor cell line NCB20.

We examined the effect of chronic opiate treatment on the alpha 2-adrenergic receptor binding of both the agonist [3H]clonidine and the antagonist [3H]yohimbine in the cerebral cortex and kidney of rats. In addition, we demonstrated the presence of an adrenergic receptor of the alpha 2 type on the neurotumor cell line NCB20 and used this cell line as a model for studying the interaction between the opiate and alpha 2-adrenergic systems. In all the three above systems, chronic opiate treatment did not modify the number or the affinity of alpha 2-adrenergic receptors.

Animals↗
PubMed1983

Reversal of morphine-induced catalepsy in the rat by narcotic antagonists and their quaternary derivatives.

The effects of the pure narcotic antagonists, naloxone and naltrexone, and their quaternary derivatives, methylnaloxone and methylnaltrexone, were examined in reversing the catalepsy induced by morphine in rats. Morphine, 20 mg/kg, induced rigid catalepsy which attained a peak effect (as manifested by duration of catalepsy) at 60-120 min and progressively declined thereafter. Both naloxone and naltrexone, administered subcutaneously 40 min after the injection of morphine, dose-dependently reduced the duration of the catalepsy at doses of 10-30 micrograms/kg. Methylnaloxone also completely reversed the catalepsy at doses of 1-10 mg/kg, when given subcutaneously. In contrast, the subcutaneous administration of methylnaltrexone only partially reversed the catalepsy at doses up to 56 mg/kg 60-90 min post-morphine. The extent of the reversal of catalepsy produced by methylnaltrexone tended to increase with time. Methylnaltrexone, administered into the cerebral ventricles 70 min after the injection of morphine, completely suppressed the catalepsy with an ED50 of approx. 1 microgram/kg when tested at 90 min after morphine. These results indicate that opiate-induced catalepsy is predominantly mediated at sites within the central nervous system. Methylnaltrexone is about 10,000 times more potent in reversing catalepsy when administered centrally than when administered peripherally. Thus, methylnaltrexone may be useful in defining sites of opiate action and in therapeutically blocking undesirable peripheral effects of opiate analgesics.

Animals↗
PubMed1982

Cialit: a study.

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Bacteria↗
PubMed1982

Renal blood-flow changes during renal nerve stimulation in rats treated with alpha-adrenergic and dopaminergic blockers.

1. Blood flow through the inner cortex and outer medulla of the rat kidney was measured by the hydrogen wash-out technique. 2. Renal nerve stimulation caused vasoconstriction in both cortex and medulla. This constriction was abolished or reduced by phenoxybenzamine (9 mumole/kg I.V.), phentolamine (100 n-mole/kg) or prazosin (1.5 mumole/kg). 3. After prazosin (6 mumole/kg I.V.), renal nerve stimulation caused small but significant renal cortical vasodilatation. This vasodilatation was reversed by sulpiride (0.7 mumole kg-1 min-1), but was unaffected by propranolol (10 mumole/kg) or atropine (4.3 mumole/kg). 4. These results indicate the existence of dopaminergic vasodilator nerves to the renal cortex of the rat.

Adrenergic alpha-Antagonists↗
PubMed1980

Pulmonary oedema after the administration of intravenous salbutamol and ergometrine. Case report.

A patient in premature labour was treated with an intravenous salbutamol infusion for 56 hours before delivery by Caesarean section. Ergometrine was given 45 minutes after the salbutamol infusion was stopped and the patient developed pulmonary oedema postoperatively. We disucss the pharmacological implications of the interaction between these drugs and their effect on the sympathetic system.

Adult↗