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Biomedical subjects

F J Martin

Publications and source records attributed to F J Martin.

At least 37 records · Page 2Linked to original sources
PubMed1992

Sterically stabilized liposomes. Reduction in electrophoretic mobility but not electrostatic surface potential.

The electrophoretic mobility of liposomes containing a negatively charged derivative of phosphatidylethanolamine with a large headgroup composed of the hydrophilic polymer polyethylene glycol (PEG-PE) was determined by Doppler electrophoretic light scattering. The results show that this method is improved by the use of measurements at multiple angles to eliminate artifacts and that very small mobilities can be measured. The electrophoretic mobility of liposomes with 5 to 10 mol% PEG-PE is approximately -0.5 mu ms-1/Vcm-1 regardless of PEG-PE content compared with approximately -2 mu ms-1/Vcm-1 for similar liposomes but containing 7.5% phosphatidylglycerol (PG) instead of PEG-PE. Measurements of surface potential by distribution of an anionic fluorescent probe show that the PEG-PE imparts a negative charge identical to that by PG, consistent with the expectation of similar locations of the ionized phosphate responsible for the charge. The reduced mobility imparted by the surface bound PEG is attributed to a mechanism similar to that described for colloidal steric stabilization: hydrodynamic drag moves the hydrodynamic plane of shear, or the hydrodynamic radius, away from the charge-bearing plane, that of the phosphate moities. An extended length of approximately 50 A for the 2,000 molecular weight PEG is estimated from the reduction in electrophoretic mobility.

Biophysical Phenomena↗
PubMed1992

Prolonged systemic delivery of peptide drugs by long-circulating liposomes: illustration with vasopressin in the Brattleboro rat.

The value of novel systemically long-circulating liposomes to prolong the duration of an antidiuretic hormone, arg8-vasopressin (VP), was investigated as a representative of low molecular weight peptides with rapid clearance. Cholesterol content was found to have a controlling effect on VP release in serum. Three types of liposomes were selected for urine production measurements in VP deficient Brattleboro rats. One contained phosphatidylserine (PS), which was rapidly cleared from the circulation. In the other two liposomes, the PS component was replaced by either phosphatidylglycerol or a novel phospholipid derivatized with polyethylene glycol (PEG); both showing prolonged circulation. Free VP (up to 8 micrograms/kg) gave reduced urine production for less than 24 hr. The PG formulation exhibited a dose-dependent prolonged duration of bioactivity of up to 4 days. Substitution of PEG-PE resulted in a 2-day delay followed by a prolonged duration of bioactivity for over 4 days. The duration of the prolonged bioactivity was not dose dependent but the amplitude was. This is attributed to VP release from liposomes which have distributed intact to another compartment without having been taken up by the RES. By balancing liposome circulation time, release rate, and dose, long-circulating liposomes can be applied to prolong the biological activity of a therapeutic peptide.

Animals↗
PubMed1991

Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times.

Therapeutic applications of intravenously injected liposomes have been limited by their rapid clearance from the bloodstream and their uptake by the macrophage cells of the liver and spleen (RES). Recently, however, liposomes which substantially evade the rapid uptake by the RES have been introduced. Since these liposomes exhibit dramatically different pharmacokinetics and biodistribution, new therapeutic opportunities have appeared. These include enhanced efficacy of antineoplastic agents against tumors, sites of inflammation, and targeting ligand-coupled liposomes to extravascular targets. Despite extensive experimental work, the mechanism underlying the ability of liposomes to avoid the rapid uptake by the RES is still not fully understood. Our approach is an alternative to seeking the answers in complex differential interactions of liposomes with various components of blood. We believe that the effect can be easily explained, at least in qualitative terms, by the fundamental principles of colloid stability. In this communication, we propose that steric stabilization of liposomes is responsible for their prolonged circulation times. We propose that stabilization results from local surface concentration of highly hydrated groups that sterically inhibit both electrostatic and hydrophobic interactions of a variety of blood components at the liposome surface.

Animals↗
PubMed1991

Assessment of vision in infants and children.

An understanding of vision development is important in the assessment of visual problems. The authors look at this factor and outline testing procedures useful in the assessment of vision in the paediatric patient.

Child↗
PubMed1990

Intraocular lacrimal gland choristoma.

There have been nine previously reported cases of intraocular lacrimal gland choristoma. This case report is of an infant with an intraocular lacrimal gland choristoma which was managed conservatively for a 19-month period until the onset of glaucoma. Tumour biopsy was initially performed because until this time the tumour's behaviour suggested it was not malignant. The latter was confirmed on biopsy, however hypotony resulted following the surgical intervention.

Biopsy↗
PubMed1989

The impact of discussion of non-medical problems in the physician's office.

To determine the impact of discussion of non-medical problems with the physician, patients with at least one chronic illness who were taking medication were interviewed in their family doctor's office. Of 149 patients interviewed, 90.6% reported at least one non-medical problem. Half (51%) of those patients with a problem had discussed it with their doctor. More than half (55%) of those patients discussing a problem reported that the discussion was helpful. Patient compliance and satisfaction were positively associated with 'helpful' discussion, but not with discussion per se. In particular, the two aspects of doctor-patient communication which were significantly associated with feeling helped were: 'Doctor tells me all I want to know about my illness' and 'Doctor gives me a chance to say what is really on my mind'. Both factors reflect care which is oriented to patient concerns. The study results provide support for a patient-centred approach to care.

Adult↗
PubMed1986

Large liposome agglutination technique for the serological detection of syphilis.

In response to tissue invasion by Treponema pallidum, an antibody complex, called reagin, appears in the serum of the syphilitic patients. Reagin has the ability to combine with cardiolipin, therefore, cardiolipin has traditionally been used as the antigen in different test configurations for the serological detection of syphilis: the VDRL (Venereal Disease Research Laboratory) flocculation test and the RPR (rapid plasma reagin) test. Here we introduce a liposome preparation composed of cardiolipin, lecithin and cholesterol and containing a colored dye which upon mixing with syphilitic serum on a slide or a plastic card results in clearly visible liposome agglutination. We show that the liposomes in the size range of 1-10 micron are essential for proper sensitivity. The liposomes are colored with either a water-soluble dye entrapped in the aqueous space of liposomes or a lipophilic dye embedded in the membrane. By virtue of the liposome size and coloration the agglutination pattern is easily visible within 3-5 min without the use of a mechanical rotator. The approach described here can be extended to the detection of other antibodies and polyvalent antigens.

Agglutination Tests↗
PubMed1985

Concurrent pineoblastoma and unilateral retinoblastoma: a forme fruste of trilateral retinoblastoma?

A 10-month-old boy who presented with strabismus and symptoms of intracranial hypertension was found to have a pineoblastoma and a unilateral ocular retinoblastoma. Despite enucleation of the eye, subtotal removal of the pineoblastoma, and craniospinal axis irradiation, the patient died 6 months later from disseminated intracranial neoplasm. As there was no clinical evidence of bilateral retinoblastoma, this case may represent a forme fruste of the trilateral retinoblastoma complex. The clinicopathological features of this unusual syndrome are reviewed.

Brain Neoplasms↗
PubMed1983

Association of ganglioside-protein conjugates into cell and Sendai virus. Requirement for the HN subunit in viral fusion.

A method is described for preparing a covalent conjugate of proteins, in particular antibodies and their fragments, with gangliosides in the micellar form. The protein-ganglioside conjugate is associated with ganglioside micelles and can be separated from free protein by molecular sieve chromatography. Conjugates can irreversibly transfer from the micelle to a cell membrane of choice, and the protein portion be identified as a new surface antigen. The successful application of this methodology has been demonstrated with three biological systems. Rabbit IgG-ganglioside conjugate has been transferred to human or sheep erythrocytes, which have been hemagglutinated with goat anti-rabbit IgG. Erythrocytes modified with ganglioside-anti-H2Kk have been shown to adhere to monolayers of L929 mouse fibroblasts which express H2Kk-antigen. Mouse monoclonal anti-glycophorin ganglioside conjugate can associate with Sendai virus and confer upon the virus the ability to agglutinate and hemolyse desialylated human erythrocytes. Using the anti-glycophorin conjugate, we demonstrated that the HN subunit, which is normally responsible for viral binding, appears also to be essential for fusion activity, because its destruction eliminates hemolysis and fusion, but not agglutination, by the conjugate-modified virus.

Animals↗
PubMed1982

Irreversible coupling of immunoglobulin fragments to preformed vesicles. An improved method for liposome targeting.

Rabbit Fab' antibody fragments were covalently couple to preformed large unilamellar vesicles using a new sulfhydryl-reactive phospholipid derivative N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine (MPB-PE). A highly efficient reaction between the sulfhydryl group on each Fab' fragment and the maleimide moiety of MPB-PE molecules incorporated at a low concentration in vesicle bilayers led to the formation of a highly stable Fab'-vesicle linkage. Coupling ratios in excess of 250 micrograms of Fab'/mumol of vesicle phospholipid were reproduciably obtained without vesicle aggregation. Bound Fab' fragments did not elute from vesicles in serum or in the presence of reducing agents (dithiothreitol or mercaptoethanol). Vesicles bearing Fab' fragments raised against specific human erythrocyte surface determinants bound selectively to human erythrocytes under physiological conditions (isotonic medium containing 50% human serum, pH 7.4) with minimal leakage of vesicle contents. Advantages of the present coupling method are discussed in relationship to our effects to optimize the properties of liposomes as a carrier system.

Animals↗
PubMed1981

Immunospecific targeting of liposomes to cells: a novel and efficient method for covalent attachment of Fab' fragments via disulfide bonds.

An efficient method for covalently cross-linking 50K Fab' antibody fragments to the surface of lipid vesicles is reported. Coupling up to 600 microgram of Fab'/mumol of phospholipid (about 6000 Fab' molecules per 0.2-micrometer vesicle) is achieved via a disulfide interchange reaction between the thiol group exposed on each Fab' fragment and a pyridyldithio-derivative of phosphatidylethanolamine present in low concentration in the membranes of preformed large unilamellar vesicles. The coupling reaction is efficient, proceeds rapidly under mild conditions, and yields well-defined products. Each vesicle-linked Fab' fragment retains its original antigenic specificity and full capacity to bind antigen. We have used Fab' fragments, coupled to vesicles by this method, to achieve immunospecific targeting of liposomes to cells in vitro. Vesicles bearing antihuman erythrocyte Fab' fragments bind quantitatively to human erythrocytes (at multiplicities up to 5000 0.2-micrometer vesicles per cell) while essentially no binding is observed to sheep or ox red blood cells. Vesicle-cell binding is stable over a pH range from 6 to 8 and is virtually unaffected by the presence of human serum (50%). Cell-bound vesicles retain their aqueous contents and can be eluted intact from cells by treatment with reducing agents (dithiothreitol or mercaptoethanol) at alkaline pH.

Animals↗
PubMed1977

Management of persistent filtering cicatrix following cataract extraction.

We used a safe and simple surgical technique in the management of persistent filtering cicatrices after cataract extraction. The edematous, friable filtering cicatrix was excised entirely and a healthy fornix-based conjunctival flap was sutured over the fistula. Invariably, the fistula was very small, usually only large enough to admit a 27-gauge needle. Of the 27 eyes treated with this technique, there were two failures, but no other complications.

Aged↗
PubMed1976

Phospholipid exchange between bilayer membrane vesicles.

The turbidity of lipid vesicles, freshly prepared by sonicating purified dimyristoyllecithin (DML) in dilute KCl solutions, was measured as a function of time at various temperatures. A sharp maximum in the rate of increase of turbidity is found just above the crystal:liquid-crystal phase transition temperature (Tm). The initial rate of turbidity increase is first order with respect to DML concentration. Electron and light microscopy reveal large vesicles which are not present before incubation or after incubation at temperatures far from the Tm. When temperature, rather than time, is the independent variable, a sharp drop in turbidity is seen at the Tm. The magnitude of this drop and the temperature at which it occurs were used to measure the rate of lipid transfer between vesicles composed of different lipids. A mixture of DML vesicles and dipalmitoyllecithin (DPL) vesicles exhibits sharp drops in turbidity at 24 and 41 degrees, the corresponding Tm's. With time, the magnitude of the transition at 24 degrees decreases while that which was originally at 41 degrees moves to lower temperatures and increases in magnitude. At equilibrium there is a single transition at 32.5 degrees characteristic of vesicles composed of equimolar DPL and DML. The rate at which equilibrium is approached increases at around 24 degrees and again around 41 degrees. These observations indicate that vesicles are in equilibrium with monomolecular lipid, the concentration of the latter being higher the shorter the lipid acyl group or the smaller the vesicle. DML molecules are therefore lost from small vesicles to large vesicles (DML system) or lost from DML vesicles to DML-DPL vesicles (mixed system). When DML vesicles containing a few percent brain gangliosides were studied, different behavior was observed; the initial rate of increase of turbidity becomes second order in lipid concentration, and the rate constant increases with increasing concentrations of KCl. The kinetic order, coupled with the fact that electrolyte reduces intervesicle electrostatic repulsion, argues that in this situation the mechanism of vesicle growth requires vesicle collision.

Binding Sites↗
PubMed1976

Lipid vesicle-cell interactions. I. Hemagglutination and hemolysis.

The interaction of lipid vesicles (liposomes) of several different compositions with erythrocytes has been investigated. Lecithin liposomes, rendered positively charged with stearylamine, exhibit potent hemagglutination activity in media containing low concentrations of electrolytes. The hemagglutination titer is found to be a linear function of the zeta potential of the lipid vesicles. Hemagglutination is reduced when the surface potential of the cells is made more positive by pH adjustment or enzyme treatment. Similarly, hemagglutination is reduced by increasing concentrations of electrolytes. Hemagglutination is examined theoretically and is shown to be consistent with vesicle-cell interactions that are due to only electrostatic forces. Vesicles containing lysolecithin in addition to lecithin and stearylamine cause lysis of erythrocytes, provided the lipids of the vesicles are above the crystal-liquid crystal phase transition temperature. In addition, hemolysis requires close juxtaposition of the vesicle to the cell membrane; vesicles precoated with antibodies exhibit severely diminished hemolytic activities, only a small fraction of which can be attributed to a reduction in hemagglutination titer. Evidence is presented indicating that a single vesicle is sufficient to lyse one cell. With regard to hemagglutination and hemolysis, lipid vesicles of simple composition mimic paramyxoviruses such as Sendai virus.

Cell Aggregation↗