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Biomedical subjects

M Bloom

Publications and source records attributed to M Bloom.

At least 37 records · Page 2Linked to original sources

Fragmentation of phospholipid bilayers by myelin basic protein.

Human myelin basic protein (MBP) is shown to disrupt multilamellar phosphatidylcholine bilayers into small lipoprotein particles in a manner similar to the cytolytic peptide melittin (Dufourc, E. J., Smith, I. C. P., & Dufourcq, J. (1986) Biochemistry 25, 6448-6455). This bilayer fragmentation, as monitored by 31P nuclear magnetic resonance, is temperature-dependent and completely inhibited by the presence of small amounts of negatively charged phosphatidylserine. The stabilizing property of phosphatidylserine is lost with the neutralization of its negative charges upon membrane binding of cationic species such as calcium ions. No MBP-induced fragmentation is observed with bilayers of negative or zwitterionic lipid mixtures which mimic the myelin lipid composition. The membrane fragmentation observed in vitro in the presence of MBP could play a role in vivo in demyelinating diseases.

Calcium↗

Models of stratum corneum intercellular membranes: 2H NMR of macroscopically oriented multilayers.

Deuterium NMR was used to characterize model membrane systems approximating the composition of the intercellular lipid lamellae of mammalian stratum corneum (SC). The SC models, equimolar mixtures of ceramide:cholesterol:palmitic acid (CER:CHOL:PA) at pH 5.2, were contrasted with the sphingomyelin:CHOL:PA (SPM:CHOL:PA) system, where the SPM differs from the CER only in the presence of a phosphocholine headgroup. The lipids were prepared both as oriented samples and as multilamellar dispersions, and contained either perdeuterated palmitic acid (PA-d31) or [2,2,3,4,6-2H5]CHOL (CHOL-d5). SPM:CHOL:PA-d31 formed liquid-ordered membranes over a wide range of temperatures, with a maximum order parameter of approximately 0.4 at 50 degrees C for positions C3-C10 (the plateau region). The quadrupolar splitting at C2 was significantly smaller, suggesting an orientational change at this position, possibly because of hydrogen bonding with water and/or other surface components. A comparison of the longitudinal relaxation times obtained at theta = 0 degrees and 90 degrees (where theta is the angle between the normal to the glass plates and the magnetic field) revealed a significant T1Z anisotropy for all positions. In contrast to the behavior observed with the SPM system, lipid mixtures containing CER exhibited a complex polymorphism. Between 20 and 50 degrees C, a significant portion of the entire membrane (as monitored by both PA-d31 and CHOL-d5) was found to exist as a solid phase, with the remainder either a gel or liquid-ordered phase. The proportion of solid decreased as the temperature was increased and disappeared entirely above 50 degrees C. Between 50 and 70 degrees C, the membrane underwent a liquid-ordered to isotropic phase transition. These transitions were reversible but displayed considerable hysteresis, especially the conversion from a fluid phase to solid. The order profiles, relaxation behavior, and angular dependence of these parameters suggest strongly that both the liquid-ordered CER- and SPM-membranes are bilayers. The unusual phase behavior observed for the CER-system, particularly the observation of solid-phase lipid at physiological temperatures, may provide insight into the functioning of the permeability barrier of stratum corneum.

Animals↗

Transcranial Doppler ultrasonography with induction of anesthesia for neurosurgery.

Intracranial hypertension can occur with induction of anesthesia; however, the clinical significance of this is unclear. We used transcranial Doppler (TCD) ultrasonography in neurosurgical patients during induction of anesthesia and endotracheal intubation to assess the incidence of high intracranial pressure (ICP) waveforms and to correlate TCD observations with specific anesthetics and anesthetic regimens. The middle cerebral artery was monitored by TCD during induction of anesthesia and endotracheal intubation in 196 patients undergoing elective neurosurgery. Middle cerebral artery blood flow velocity (MCABFV) and physiologic data were observed continuously and recorded at the following times: preinduction, induction, intubation, and postintubation. Induction with thiopental or etomidate decreased MCABFV, intubation increased MCABFV, and postintubation ventilation decreased MCABFV. MCABFV was higher throughout the induction sequence in the 92 patients with tumors. Although there were numerous individual exceptions, changes in mean arterial pressure correlated statistically with changes in MCABFV. No patient had an end-diastolic flow velocity of 0. We reached the following conclusions: (a) TCD is a straightforward modality that can be used to monitor dynamic cerebrovascular events during induction of anesthesia; (b) MCABFV is increased with brain tumors; (c) thiopental and etomidate rapidly decrease and intubation rapidly increases MCABFV; and (d) routine TCD monitoring for high ICP waveforms during anesthetic induction for routine elective neurosurgery appears to be unwarranted.

Adult↗

Response to specific Centruroides sculpturatus antivenom in 151 cases of scorpion stings.

Review was made of the symptoms, treatment and outcome of 151 cases of severe envenomation by the scorpion Centruroides sculpturatus treated with antivenom, 1988-1989. The most frequent symptoms were restlessness, nystagmus, paresthesiae, hypersalivation, fasciculation, blurred vision and dysphagia with an average of four symptoms. Medications before antivenom, given to about half of the subjects, included antihistamines, sedatives, analgesics and epinephrine. In 71% of patients, symptoms were relieved within 30 minutes of receiving one vial. Immediate hypersensitivity reactions occurred in 8%, but were generally mild. Skin tests had a sensitivity of 96% and specificity of 68%. Delayed reactions were not addressed. In conclusion, the antivenom appears safe and effective.

Adolescent↗

Evidence for two pools of cholesterol in the Acholeplasma laidlawii strain B membrane: a deuterium NMR and DSC study.

Recent investigations have indicated that there exists a well-defined range of membrane hydrocarbon order compatible with good growth of the microorganism Acholeplasma laidlawii B [Monck, M., Bloom, M., Lafleur, M., Lewis, R. N. A. H., McElhaney, R. N., & Cullis, P. R. (1992) Biochemistry 31, 10037-10043]. Since cholesterol increases hydrocarbon order in membranes, it was of interest to examine the effect of cholesterol on the hydrocarbon order and growth characteristics of A. laidlawii B. Cholesterol is normally absent from A. laidlawii membranes since it is neither biosynthesized nor required for the growth or survival of the microorganism. However, cholesterol will be incorporated into the membrane if exogenously supplied to the A. laidlawii culture. For membranes prepared from cells grown in the presence of cholesterol, chemical determinations indicated cholesterol represented as much as 40 mol% of the total membrane lipid. However, 2H NMR order parameter measurements and DSC studies of the same membrane preparation suggested that cholesterol was present at significantly lower levels (approximately 10-15 mol%) in the membrane lipid bilayer. Further incorporation of cholesterol into the A. laidlawii lipid bilayer was found to occur with an increase in temperature or by lyophilization and rehydration at high temperatures, suggesting that sterol present in a separate pool in the membrane preparation could then gain access to the bilayer. 2H NMR spectra of A. laidlawii membrane preparations containing deuterium-labeled cholesterol indicate that the bulk of the cholesterol present in this separate pool is in a solid form.

Acholeplasma laidlawii↗

Modulation of eicosanoid and histamine release from human dispersed lung cells by terfenadine.

Terfenadine is an H1-blocker that may have antiallergic properties. A study was carried out to examine the ability of terfenadine to inhibit the release of histamine and arachidonic-acid-derived mediators from human lung cells. Cells were dispersed from fresh human lung tissue obtained from four accident victims whose hearts were donated for transplantation and four lung cancer resections. Cells were dispersed by enzymatic digestion with type XIV protease and chymopapain, and this resulted in a cell population containing approximately 5% mast cells. The remaining cells were mainly macrophages. The cells were challenged with anti-IgE at a 1/1000 dilution. Cells were challenged without terfenadine and after a preincubation of 0.1, 1, and 10 mumol terfenadine. The release of PGD2 and LTC4/D4 was assessed with an EIA. Histamine was assayed by RIA with a monoclonal antibody against acylated histamine. A release of both eicosanoids and histamine was observed in all experiments. An inhibition of eicosanoids was observed at both 1 and 10 mumol terfenadine (median percentage of inhibition of PGD2: 38.00 +/- 15.65 and 56.00 +/- 13.12; median percentage of inhibition of LTC4/D4: 37.5 +/- 19.80 and 52.5 +/- 26.8). On the other hand, histamine release was not blocked by terfenadine. Terfenadine inhibits, in a dose-dependent manner, the release of eicosanoids after challenge of dispersed lung cells by anti-IgE, and this effect may have some clinical relevance.

Aged↗

Vein graft replacement of the middle cerebral artery after unsuccessful embolectomy: case report.

A forty-one-year-old man with a cavernous hemangioma of the right cavernous sinus underwent a preoperative cerebral angiogram and a balloon occlusion test of the internal carotid artery. During the operation to remove the cavernous sinus lesion, the ipsilateral electroencephalogram was found to be abnormal. An embolic occlusion of the M2 and M3 segments of the middle cerebral artery (MCA) was discovered. A platelet and thromboembolus was removed via multiple incisions, and flow was restored. The cavernous sinus lesion was removed uneventfully. At the end of the operation, the MCA was found to be reclotted. Flow was eventually restored by replacing the M2 segment of the MCA with a 2-cm saphenous vein graft. The patient recovered without any deficits of brain function and with transient deficits of Cranial Nerves III and VI. Computed tomography revealed infarcts in the temporal and parietal areas. When MCA embolectomy is unsuccessful, vein graft replacement should be considered to restore flow and to avoid major neurological deficits.

Adult↗

[Double-blind comparative study of terfenadine and cetirizine in chronic idiopathic urticaria].

Our randomised study in parallel groups, double-blind double placebo, has compared the efficacy, onset of action and safety of terfenadine and cetirizine in chronic idiopathic urticaria. Over a fourteen day period, patients of the first group received a tablet containing 120 mg of terfenadine, those of the second group a tablet containing 10 mg of cetirizine. Symptoms were assessed every two hour period for the ten first hours on the first day (D1), and before and at the end of the study by the investigators. 193 patients were included by 48 dermatologists between May 1989 and July 1990. Both groups were well matched for all general characteristics and baseline symptoms scores. The onset and the intensity of regression of symptoms (pruritus, erythema and discomfort during sleeping time) were similar in both treatment groups public physicians: improvement of pruritus in over 90% of the patients. Meanwhile the tolerability was good or excellent for dermatologists and allergologists for 92% of the patients under terfenadine against 81% of the patients under cetirizine (p < 0.05). Adverse events (fatigue and drowsiness) were significantly reported less frequently (p < 0.05) in patients on terfenadine (19%) than on cetirizine (33%). This study confirms the efficacy of terfenadine compared with cetirizine in the treatment of chronic idiopathic urticaria. Adverse events were less significant for terfenadine (n = 18) than for cetirizine (n = 29) (p < 0.05).

Adolescent↗

Models of stratum corneum intercellular membranes: the sphingolipid headgroup is a determinant of phase behavior in mixed lipid dispersions.

During formation of the intercellular membranes of mammalian stratum corneum, sphingomyelin and glucosylceramide are converted enzymatically to ceramide. To model in isolation the possible effect of such a lipid modification on the phase behavior of the ensemble, we used proton and deuterium nuclear magnetic resonance to compare an equimolar dispersion of bovine brain sphingomyelin, cholesterol, and perdeuterated palmitic acid (at pH 6.2), with an equivalent dispersion in which bovine brain ceramide was substituted for sphingomyelin. While the sphingomyelin dispersions remain in a homogeneous fluid lamellar phase from 20-75 degrees C under these conditions, those containing ceramide display complex polymorphism.

Ceramides↗

Influence of lipid composition on the orientational order in Acholeplasma laidlawii strain B membranes: a deuterium NMR study.

2H NMR techniques have recently been developed to determine the complete orientational order profile of lipid bilayers employing lipids containing perdeuteriated palmitic acid [Lafleur, M., Fine, B., Sternin, E., Cullis, P.R., & Bloom, M. (1989) Biophys. J. 56, 1037-1041]. In this work, these techniques have been applied to study order profiles in intact membranes derived from Acholeplasma laidlawii strain B. It is shown that complete orientational order profiles can be readily obtained from the intact membranes of A. laidlawii B grown on equimolar amounts of perdeuteriated palmitic acid and a nondeuteriated fatty acid of varying length and unsaturation. By variation of the fatty acid composition employing mixtures of perdeuteriated palmitic acid with myristic, elaidic, oleic, or linoleic acid, a range of hydrocarbon order compatible with high rates and extents of cell growth has been obtained where the average order parameter, mean value of S, varies over the range 0.140-0.176. This same variation in order is seen for liposomes derived from total lipids extracted from these intact membranes. 2H NMR studies on liposomes composed of individual species of the extracted lipids indicate that modulation of the membrane lipid headgroup composition has the potential to play an important role in maintaining the membrane order within this range.

Acholeplasma laidlawii↗

Combined influence of cholesterol and synthetic amphiphillic peptides upon bilayer thickness in model membranes.

Deuterium (2H) NMR was used to study bilayer hydrophobic thickness and mechanical properties when cholesterol and/or synthetic amphiphillic polypeptides were added to deuterated POPC lipid bilayer membranes in the liquid-crystalline (fluid) phase. Smoothed acyl chain orientational order profiles were used to calculate bilayer hydrophobic thickness. Addition of 30 mol% cholesterol to POPC at 25 degrees C increased the bilayer thickness from 2.58 to 2.99 nm. The peptides were chosen to span the bilayers with more or less mismatch between the hydrophobic peptide length and membrane hydrophobic thickness. The average thickness of the pure lipid bilayers was significantly perturbed upon addition of peptide only in cases of large mismatch, being increased (decreased) when the peptide hydrophobic length was greater (less) than that of the pure bilayer, consistent with the "mattress" model of protein lipid interactions (Mouritsen, O.G., and M. Bloom. 1984. Biophys. J. 46:141-153). The experimental results were also used to examine the combined influence of the polypeptides and cholesterol on the orientational order profile and thickness expansivity of the membranes. A detailed model for the spatial distribution of POPC and cholesterol molecules in the bilayers was proposed to reconcile the general features of these measurements with micromechanical measurements of area expansivity in closely related systems. Experiments to test the model were proposed.

Biomechanical Phenomena↗

Temperature-reversible eruptions of vesicles in model membranes studied by NMR.

Deuterium (2H) and phosphorus (31P) nuclear magnetic resonance (NMR) and freeze-fracture electron microscopy were used to study spontaneous vesiculation in model membranes composed of POPC:POPS with or without cholesterol. The NMR spectra indicated the presence of a central isotropic line, the intensity of which is reversibly and linearly dependent upon temperature in the L alpha phase, with no hysteresis when cycling between higher and lower temperatures. Freeze-fracture microscopy showed small, apparently connected vesicles that were only present when the samples were frozen (for freeze-fracture) from an initial temperature of 40-60 degrees C, and absent when the samples are frozen from an initial temperature of 20 degrees C. Analysis of motional narrowing was consistent with the isotropic lines being due to lateral diffusion in (and tumbling of) small vesicles (diameters approximately 50 nm). These results were interpreted in terms of current theories of shape fluctuations in large unilamellar vesicles which predict that small daughter vesicles may spontaneously "erupt" from larger parent vesicles in order to expel the excess area created by thermal expansion of the bilayer surface at constant volume. Assuming that all the increased area due to increasing temperature is associated with the isotropic lines, the NMR results allowed a novel estimate of the coefficient of area expansion alpha A in multilamellar vesicles (MLVs) which is in good agreement with micromechanical measurements upon giant unilamellar vesicles of similar composition. Experiments performed on unilamellar vesicles, which had been placed upon glass beads, confirmed that alpha A determined in this way is unchanged compared with the MLV case. Addition of the highly positively charged (extrinsic) myelin basic protein (MBP) to a POPC:POPS system showed that membrane eruptions of the type described here occur in response to the presence of this protein.

Biophysical Phenomena↗

Probe orientation in contact Nd:YAG laser cyclophotocoagulation.

We investigated the effect of the angle orientation of the probe during Nd:YAG transscleral cyclophotocoagulation. We found, based on histologic evaluation of the ciliary processes and surrounding structures, that the angle at which the probe was placed on the eye was critical. A probe angulation as little as 15 degrees off the perpendicular destroyed sites less than optimal for achieving the goal of decreasing aqueous humor production.

Aqueous Humor↗

Calcium binding by phosphatidylserine headgroups. Deuterium NMR study.

The binding of calcium to headgroup deuterated 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphoserine (POPS) was investigated by using deuterium magnetic resonance in pure POPS membranes and in mixed 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphocholine (POPC)/POPS 5:1 (m:m) bilayers. Addition of CaCl2 to pure POPS bilayers led to two component spectra attributed, respectively, to liquid-crystallin POPS (less than 15 kHz) and POPS molecules in the calcium-induced dehydrated phase (cochleate) (approximately 120 kHz). The liquid-crystalline component has nearly disappeared at a Ca2+ to POPS ratio of 0.5, indicating that, under such conditions, most of the POPS molecules are in the precipitated cochleate phase. After dilution of the POPS molecules in zwitterionic POPC membranes (POPC/POPS 5:1 m:m), single component spectra characteristic of POPS in the liquid-crystalline state were observed in the presence of Molar concentrations of calcium ions (Ca2+ to POPS ratio greater than 50), showing that the amount of dehydrated cochleate PS-Ca2+ phase, if any, was low (less than 5%) under such conditions. Deuterium NMR data obtained in the 15-50 degrees C temperature range with the mixed PC/PS membranes, either in the absence or the presence of Ca2+ ions, indicate that the serine headgroup undergoes a temperature-induced conformational change, independent of the presence of Ca2+. This is discussed in relation to other headgroup perturbations such as that observed upon change of the membrane surface charge density.

Calcium↗

The six languages of social work.

This article describes the six languages that scientifically minded and practice-competent social workers need to be fluent in: the lay language of the client, the abstract language of the theorist, the empirical and often quantitative language of the researcher, the categorical language of the information scientist, the technical terminology or jargon used by helping professionals, and the preferential language that conveys values. It is the thesis of this article that social workers need multilingual and translingual proficiency in moving rapidly back and forth among these languages for maximum effectiveness and humane service.

Humans↗