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Biomedical subjects

J D Millar

Publications and source records attributed to J D Millar.

At least 19 recordsLinked to original sources
PubMed1997

The potential transmission of infectious agents by semen packaging during storage for artificial insemination.

Plastic straws, of a type widely used for semen cryopreservation, sealed using three different methods, (PVA powder, plastic spheres and plasticine modelling clay) were tested for leakage of low molecular weight dye (methylene blue), bacteria (Escherichia coli) and virus (Newcastle disease virus). Leakage was found to be dependent on the method used to fill the straws. Straws filled using a traditional 'dip and wipe' method and sealed with PVA powder demonstrated a significant degree of methylene blue leakage (0.0269% of the total straw contents) probably associated with contamination of the powder sealing plug. Straws filled using an aseptic filling technique showed no detectable leakage of any agent with any of the sealing methods. This study highlights the need to establish good-practice guidelines for the packaging of semen collected for freezing and future AI from non-domestic livestock where disease-free status cannot be guaranteed and unsophisticated technology is used.

Animals↗
PubMed1996

Surface area and volume measurements for ram and human spermatozoa.

Surface area and volume measurements were made for ram and human spermatozoa. Measurements were made using different techniques in an attempt to confirm estimates arrived at by independent methodologies. Sperm head projected surface areas were calculated from published formulae using linear micrometry measurements or were obtained directly by image analysis. Total surface areas were calculated as twice the projected head area plus the flagella area, estimated from published dimensions. Spermatozoon surface area was also measured from electron micrographs using a stereological method. Micrometric methods gave values of 135 microns2 for ram spermatozoa and 106 microns2 for human spermatozoa. Stereology methods gave values of 142 microns2 for ram spermatozoa and 106.5 microns2 for human spermatozoa, offering good agreement between the two methods. Sperm volumes were estimated by stereology and by radiolabel volume exclusion methods. From stereology, ram sperm volume was 13.3 microns3 and human sperm volume was 22.2 microns3. From the volume exclusion method, ram sperm volume was estimated as 25 microns3. Attempts to measure total volume and water volume simultaneously using and adaptation of this method were unsuccessful. Separate estimation of water volume for ram spermatozoa gave a value or 12.8 microns3, suggesting a 50% water space. Results from this study are compared with existing published values.

Animals↗
PubMed1995

The presence of water channel proteins in ram and human sperm membranes.

Ram and human spermatozoa have a high coefficient of osmotic water permeability (Pf) with a low activation energy (Ea), suggesting the presence of water channels within their plasma membranes. Sperm membranes were examined for the presence of two known water channel proteins, CHIP28 and glucose transporters belonging to the GLUT family of proteins. The water permeability of ram spermatozoa was not inhibited by mercuric chloride to which the CHIP28 channel is sensitive. The CHIP28 protein was not located in western blots of ram sperm membrane preparations that used an anti-CHIP28 antibody. The water permeability of ram and human spermatozoa was inhibited in the presence of phloretin, an inhibitor of glucose transport. Rabbit spermatozoa, which have a low Pf and a high Ea value, suggesting a non-porous membrane, were unaffected by phloretin. These results indicate that the erythrocyte and proximal tubule water channel, CHIP28, is not present in sperm membranes but that sperm membrane glucose transporters may have a secondary water channel function.

Animals↗
PubMed1994

Calculated optimal cooling rates for ram and human sperm cryopreservation fail to conform with empirical observations.

The permeability coefficient to water (Lp) and its associated activation energy (Ea) were measured for ram (8.47 microns/min/atm at 25 degrees C, 1.06 kcal/mol) and human (2.89 microns/min/atm at 30 degrees C, 1.93 kcal/mol) spermatozoa. By use of these figures, predictive water loss curves were calculated, from published equations, for different cooling rates from 100 degrees C/min to 100,000 degrees C/min. The calculated curves show that ram spermatozoa cooled at even the fastest rate would be in osmotic equilibrium by -20 degrees C, and human spermatozoa cooled at rates up to 10,000 degrees C/min would be in equilibrium by -15 degrees C. If the nucleation temperature for spermatozoa is taken to be between -20 degrees C and -30 degrees C, then ram and human spermatozoa cooled at these rates would apparently not exhibit any intracellular freezing. There is a significant discrepancy between these calculated optimal cooling rates and the published empirically derived optimal rates of 50 degrees C/min for ram and 10 degrees C/min for human. The failure of ram and human spermatozoa to conform with the established and previously successful model for prediction of optimal cooling rates suggests that damage sustained at high cooling rates may be unrelated to intracellular ice formation.

Animals↗
PubMed1992

6-substituted decahydroisoquinoline-3-carboxylic acids as potent and selective conformationally constrained NMDA receptor antagonists.

We have prepared a series of 6-substituted decahydroisoquinoline-3-carboxylic acids, and structurally similar analogs, as potential N-methyl-D-aspartate receptor antagonists. There is a large body of evidence to support the use of such compounds as cerebroprotective agents in a variety of acute and chronic neurodegenerative disorders, where some component of glutamate-mediated excitotoxicity may exist. The compounds prepared were evaluated in vitro in both receptor binding assays ([3H]CGS19755, [3H]AMPA, and [3H]kainic acid) and in a cortical wedge preparation (versus NMDA, AMPA, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced lethality in mice. We synthesized many of the possible diastereomers of the decahydroisoquinoline nucleus in order to examine the spatial and steric requirements for affinity at the NMDA receptor and activity as NMDA antagonists. From our structure-activity relationship we identified two potent and selective NMDA receptor antagonists, the phosphonate- and tetrazole-substituted amino acids 31a and 32a, respectively, that show good activity in animals following systemic administration. For example, 31a and 32a selectively displaced [3H]CGS19755 binding with IC50S of 55 +/- 14 and 856 +/- 136 nM, respectively, and selectively antagonized responses due to NMDA in a cortical wedge preparation with IC50S of 0.15 +/- 0.01 and 1.39 +/- 0.29 microM, respectively. And compounds 31a and 32a blocked NMDA-induced lethality in mice with minimum effective doses of 1.25 and 2.5 mg/kg (intraperitoneal), respectively. These novel amino acids are among some of the most potent NMDA antagonists described thus far, and are excellent candidates for development as neuroprotective agents for a number of CNS disorders.

Animals↗
PubMed1992

Specificity and potency of N-methyl-D-aspartate glycine site antagonists and of mephenesin on the rat spinal cord in vitro.

The potency, specificity and reversibility of various presumed glycine site N-methyl-D-aspartate (NMDA) antagonists was studied on neonatal rat spinal cord using the grease gap technique. 5,7-Dichlorokynurenate was the most potent and specific glycine site antagonist among the compounds tested. On the other hand mephenesin was a weak non-specific excitatory amino acid (EAA) antagonist; reduction of the response to NMDA was not reversed by D-serine. The EAA antagonist properties of mephenesin could explain its mode of action at the cellular level. The lack of effect of D-serine alone suggests that in our experimental conditions glycine sites on spinal neurones are occupied by an endogenous ligand.

Animals↗
PubMed1991

D,L-(tetrazol-5-yl) glycine: a novel and highly potent NMDA receptor agonist.

This paper describes the pharmacological activity of D,L-(tetrazol-5-yl)glycine, a structurally novel and highly potent agonist at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor. D,L-(Tetrazol-5-yl)glycine potently displaced NMDA receptor binding to rat brain membranes as measured using [3H]CGS19755 (IC50 = 98 +/- 7 nM) and [3H]glutamate (IC50 = 36 +/- 18 nM) as ligands. D,L-(Tetrazol-5-yl)glycine did not appreciably inhibit the binding of D,L-alpha-[5-methyl-3H] amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [3H]kainate, or [3H]glycine (IC50s greater than 30,000 nM). D,L-(Tetrazol-5-yl)glycine was more potent than NMDA or cis-methanoglutamate as a depolarizing agent in the rat cortical slice, and unlike these other agents induced rapid receptor-mediated neurotoxicity. Depolarization by D,L-(tetrazol-5-yl)glycine was antagonized by LY233053, a selective NMDA receptor antagonist. D,L-(Tetrazol-5-yl)glycine was a highly potent convulsant when given to neonatal rats (ED50 = 0.071 mg/kg i.p.). Convulsions in neonatal rats or lethality in mice induced by D,L-(tetrazol-5-yl)glycine were selectively antagonized by competitive and non-competitive NMDA receptor antagonists. D,L-(Tetrazol-5-yl)glycine is a structurally novel (tetrazole-substituted) compound that is a highly potent and selective NMDA receptor agonist. D,L-(Tetrazol-5-yl)glycine could be used to probe further NMDA receptor function in vitro and in vivo.

Animals↗
PubMed1991

Mathematical modeling and attempts to eliminate measles: a tribute to the late Professor George Macdonald.

In 1983, 5 years after the inception of an aggressive national measles elimination strategy, the United States experienced its lowest level of reported numbers of cases of measles. This accomplishment was the result of an effective vaccination strategy coupled with surveillance and control efforts by local, state, and national public health agencies. After 1983, however, the reported number of measles cases slowly increased until 1989, when the number exceeded that of 1979, the first full year of the National Measles Elimination Program. In 1990, we are experiencing epidemics throughout the United States and expect the reported number of cases of measles to exceed that of 1989. In this context, we felt it was timely to reflect on this experience in light of previous measles control efforts. In particular, we looked back to the contributions of Professor George Macdonald, which were critical to the successful elimination of measles from The Gambia in 1969. As we enter the last decade of this century, the sensible merging of mathematics and epidemiology in useful models, and the appropriate use of such models for planning, offers the best hope for achieving the elimination of measles either in this or the next century.

Child↗
PubMed1991

NMDA receptor antagonist effects of the stereoisomers of beta-cyclazocine in rats, in vivo and in vitro.

(+)- and (-)-beta-cyclazocine were examined as NMDA receptor antagonists following bath application to rat cortical wedges in vitro and i.v. administration to rat spinal cord neurones in vivo. Both isomers were found to be selective NMDA antagonists with little effect on excitations evoked by quisqualate. In vitro, IC50 values for (-)- and (+)-beta-cyclazocine against responses to 40 microM NMDA were estimated at 0.51 and greater than 100 microM, respectively. In vivo, (-)-beta-cyclazocine 0.25 mg.kg-1 reduced NMDA-evoked excitations by 70%, an effect substantially greater than that produced by (+)-beta-cyclazocine 2.5 mg.kg-1. (-)-beta-cyclazocine is the most potent NMDA antagonist benzomorphan tested to date, being about twice as potent as (-)-alpha-cyclazocine in this respect. In addition, the separation in potency exhibited by the beta-cyclazocine enantiomers as NMDA antagonists is much greater than that reported previously for the stereoisomers of the alpha-series.

Animals↗
PubMed1990

Mental health and the workplace. An interchangeable partnership.

Mental health is an important component of occupational health. The National Institute for Occupational Safety and Health (NIOSH) recognizes psychological disorders as one of the 10 leading work-related diseases and injuries (Millar, 1984). Job-related stress is receiving an increasing amount of public attention, and several studies indicate that stress-related conditions are among the most important health problems of the 1990s for people at work and outside of work.

Accidents, Occupational↗
PubMed1989

The right to know in the workplace. The moral dimension.

The makers of public policy cannot avoid the deep and often strident public controversy over the nature and scope of basic moral rights. There are persuasive defenders on both sides of the issue. Forging public policy in the absence of a broad public consensus is nothing more than the arbitrary imposition by government of some preferred, but not necessarily privileged, moral view. It hardly seems the legitimate role of a democratic government, even in the name of moral leadership, to so impose views that are deeply controversial and not capable of broad-based support by the population at large. It is better by far, for reasons of stable public policy, that we seek the painful path of building a general public consensus among the well-informed and well-meaning citizenry. If no such consensus can be achieved, then the law will, as a matter of necessity, settle the issue in the interest of the efficient discharge of general social functions. . .and that is really not a particularly unfortunate outcome.

Consumer Advocacy↗
PubMed1988

Differences in results from in vivo and in vitro studies on the use-dependency of N-methylaspartate antagonism by MK-801 and other phencyclidine receptor ligands.

We have used microelectrophoretic and intravenous administration of drugs to rat spinal cord neurones in vivo and bath application to rat cortical wedges in vitro to evaluate MK-801 and other phencyclidine (PCP) receptor ligands as N-methylaspartate (NMA) antagonists, paying particular regard to the possible use-dependent nature of their action. MK-801, 0.1-0.5 mg/kg, was a selective and long-lasting NMA antagonist. We were unable to demonstrate significant use-dependent onset of antagonism of NMA by any of the drugs in vivo. Recovery, however, for MK-801 was use-dependent. In vitro there was a gradation with MK-801 being very use-dependent, followed by (PCP), cyclazocine and ketamine, the last showing little or no use-dependence. Results of experiments modulating the in vitro environment suggest that a significant difference between the in vitro and in vivo systems was temperature. Raising the temperature of the wedge chamber from 23 to 33 degrees C reduced the use-dependence of MK-801, and lowering the temperature to 13 degrees C increased the use-dependence of PCP. The mechanism of action of PCP receptor ligands is discussed in the light of these results.

Animals↗
PubMed1988

Summary of "Proposed national strategies for the prevention of leading work-related diseases and injuries, Part 1".

Strategies for the prevention of leading occupational health problems have been proposed by the National Institute for Occupational Safety and Health (NIOSH). NIOSH prepared these strategies following publication in 1983 of its suggested list of ten leading work-related diseases and injuries. At a national symposium in 1985, occupational health experts from academia, organized labor, management, professional associations, and voluntary organizations conducted an in-depth evaluation of the prevention strategies for the first five conditions on the list: occupational lung diseases, musculoskeletal injuries, occupational cancers, severe occupational traumatic injuries, and occupational cardiovascular diseases. The strategies were then revised to incorporate improvements suggested at the symposium and were published in booklet form. A summary of the revised strategies is provided.

Accidents, Occupational↗