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Biomedical subjects

M D Owens

Publications and source records attributed to M D Owens.

7 recordsLinked to original sources

A synthetic low density lipoprotein particle capable of supporting U937 proliferation in vitro.

A synthetic LDL (sLDL) has been prepared by combining a lipid microemulsion with amphipathic peptides containing the apoprotein B receptor domain. The biological properties of sLDL have been investigated using the U937 in vitro cell proliferation assay. sLDL exhibits a concentration dependent and saturable stimulation of U937 proliferation. By utilizing different amphipathic peptides, variable proliferation is achieved, indicating a specific interaction between sLDL and the U937 LDL receptor are possible. U937 proliferation is reduced by the addition of an anti-LDL receptor antibody, indicating that sLDL is assimilated via the LDL receptor pathway. The behavior of sLDL mimics that of native LDL, and this approach represents a viable technique for the production of an sLDL particle on a large scale for research and general application.

Cell Division↗

Physicochemical properties of microemulsion analogues of low density lipoprotein containing amphiphatic apoprotein B receptor sequences.

Low density lipoprotein (LDL) has been proposed as a drug targeting vector in cancer chemotherapy, however, research has been limited due to the necessity to isolate material from plasma. In this study, the physicochemical properties of synthetic lipid microemulsions containing an amphiphatic version of the apoprotein B receptor binding sequence have been examined. The effect of peptide sequence length, lipid anchor type and location along with microemulsion lipid composition were investigated via changes in particle size and zeta potential. Size increases were related to the amphiphatic peptides lipophilic portion and too a lesser extent by amino acid sequence length. Two lipophilic anchors, retinoic acid and cholesterol, produced large size increases whilst a single anchor (retinoic acid) did not affect size. The amphiphatic peptide reversed measured zeta potential from negative to positive values in a concentration dependent manner. This was related to peptide structure and could be effected by changes in pH, indicating that the peptide was surface located and responsive to the external environment. Alteration of microemulsion lipid composition also affected physicochemical properties but to a lesser degree than changes in the amphiphatic peptide. These novel systems may represent a useful synthetic alternative to native LDL for a variety of applications.

Amino Acid Sequence↗

Topical application of garlic reduces northern fowl mite infestation in laying hens.

Northern fowl mites (NFM) are external parasites that can lower egg production and cause anemia and even death in laying hens. An experiment was conducted with New Hampshire Red and Single Comb White Leghorn laying hens. Hens were individually caged and provided a complete laying diet and water ad libitum. Hens were assigned to groups in a way that assured that treatments, within each breed, would be applied to comparable numbers of birds with light and heavy mite infestations. Each hen was sprayed around the vent with either water or 10% garlic juice in water. Spraying continued each week for 3 wk. During the fourth week, each bird was scored for the presence of NFM on its skin and feathers. A small snippet of feathers was removed from below the vent of each hen and placed in a labeled petri dish with a round, white filter paper insert. The NFM content of each dish was scored by two individuals approximately 1 h after sampling. There was no significant difference in the NFM scores for hens based on breed or future treatment. After the birds were treated for 3 wk, there was no significant difference in external NFM scores based on breed. There were significantly fewer NFM on the birds treated with garlic juice compared with controls, based on external and petri dish scoring (P < 0.002 and P < 0.04, respectively). The reduction in external NFM score was also significant (P < 0.004), with controls declining approximately 0.2 units, whereas garlic-treated hens had a 1.8-unit decrease in external NFM score. Topical application of garlic juice may be an effective way to decrease NFM in laying hens.

Administration, Topical↗

Pre-clinical development of the anti-tumour agent CB 7646, bis N-(hydroxymethyl) trimethylmelamine, a stable analogue of trimelamol.

Formulation difficulties prevented the otherwise promising clinical development of the anti-tumour agent trimelamol (TM; tris-[hydroxymethyl]trimethylmelamine]). A synthetic analogue programme resulted in the identification of CB 7646 (bis N-[hydroxymethyl]trimethylmelamine) as a compound with improved stability and favourable formulation characteristics. The in vitro and in vivo activity of CB 7646 was shown to be very similar to that of TM. In addition, curative activities were shown in the PXN/65 human ovarian cancer xenograft and the MX-1 and T-61 human breast cancer xenograft models. The effectiveness of the N-(hydroxymethyl)melamines against platinum-refractory disease was noted in the phase I clinical trial of TM. In line with this finding, the present study confirmed the effective activity of both TM and CB 7646 against various forms of platinum resistance in in vitro models. Curative activity for TM and CB 7646 was seen in the HX110P human ovarian cancer xenograft with acquired carboplatin resistance. Animal studies indicated less neurotoxicity for CB 7646 than for TM. The pharmacokinetic profile of CB 7646 indicated a decreased plasma elimination, indicative of slower in vivo degradation than for TM. CB 7646, therefore, represents a promising candidate for clinical development, designed to supersede TM.

Animals↗

Increasing group attendance on a psychiatric unit: an alternating treatments design comparison.

Compliance is a critical factor for success in the treatment of chronic psychiatric patients. Major reasons for therapeutic failure are that patients discontinue their medications, fail to keep therapist appointments, or do not participate in recommended psychosocial activities. An alternating treatments design was employed to assess the use of verbal instructions and feedback to promote group attendance on a psychiatric unit. Results showed these methods served to significantly increase group attendance but had no significant effect on patient satisfaction. These results are discussed with regard to cost-efficient methods for promoting treatment compliance with psychiatric inpatients.

Adult↗

Importance of filter structure for the trans-membrane migration studies of sperm motility.

Sperm migration through polycarbonate and nylon membrane filters was studied by the trans-membrane migration ratio method. Sperm crossed the former filters but not the latter because of the greater pore length and complexity of the relatively thick nylon membrane. Adhesion of spermatozoa to the nylon structure was also observed. Using the polycarbonate filter we were able to correlate trans-membrane migration with conventional motility and measure the effects of drugs on sperm motility.

Humans↗