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Biomedical subjects

M D Ross

Publications and source records attributed to M D Ross.

At least 19 recordsLinked to original sources

Computer-assisted three-dimensional reconstruction and simulations of vestibular macular neural connectivities.

The macular neuroepithelium is morphologically organized as a weighted neural network for parallel distributed processing of information. The network is continuous across the striola, where some type II hair cells synapse with calyces containing type I cells with tufts of opposite directional polarities. Whether other hair cell to calyx appositions that lack synapses interact because of intercellular potassium accumulation remains an open question. A functionally important inference of macular organization is that just as arrays of hair cells communicate an entire piece of information to a nerve fiber, so do macular subarrays of nerve fibers (not single units) carry the whole coded message to the brain stem. Moreover, the size of the network subarray can expand or become more limited depending upon the strength and/or duration of the input. It is the functioning of the network and its subarrays that must be understood if we are to learn how maculas carry out their work and adapt to new environments. Simulations of functioning maculas, or subparts, based on precise morphology and known physiology are useful tools to gain insights into macular information processing. The current simulations of afferent collateral electrical activity are a prelude to development of a 3-D model. The simulations demonstrate a relationship between geometry and function, with the diameter of the stem apparently being a major determinant of electrical activity transmitted to the base in the case of collaterals with short stems. Thus, while changes in synaptic number and/or size may be an important adaptive mechanism in an altered g environment, changes in diameter of the stem is another means of altering outflow. Research on the effects of microgravity should be extremely useful in examining the validity of this and other concepts of neural adaptation, since maculas are biological linear accelerometers ideally suited to the task. Maculas are also extremely interesting to study in detail because of the richness of connectivities and submicroscopic organization they present. Many of their features are common with more complex parts of the brain. It seems possible that knowledge of the three-dimensional geometric relationships operative in a functioning macula will contribute much to the understanding of the dynamics underlying more complex behavior. Computerized approaches greatly facilitate this task and provide an objective method of analysis. It is likely that, in the end, simple rules will be found to govern optimal neural architectural organization, even at higher cognitive levels. The architecture only appears complex because we do not yet grasp its meaning.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Maculae

Each otoconia polymorph has a protein unique to that polymorph.

1. Otoconia, contained within the vestibular portion of the inner ear, are mineralized by one of three polymorphs of calcium carbonate. Each otoconial polymorph contains a unique, major protein. 2. The major protein of calcitic otoconia of members of different vertebrate classes, Amphibia (African clawed frog) and Mammalia (rat), have similar molecular weights. 3. The major protein of calcitic rat otoconia and of vateritic otoconia of the gar may be calcium binding proteins. No protein from the other polymorph, aragonite, appear to have this characteristic.

Ambystoma mexicanum

Ultrastructural and cytochemical evidence for single impulse initiation zones in vestibular macular nerve fibers of rat.

Cupric ion-ferricyanide labeling methods and related ferrocyanide-stained tissues were used to locate and characterize, at the ultrastructural level, presumptive impulse initiation zones in the three types of vestibular macular nerve fibers. Large-diameter, M-type vestibular nerve fibers terminate in a calyx at the heminode, and labeling is coextensive with the base of the calyx. Intermediate, M/U-type nerve fibers have short, unmyelinated preterminal segments that sometimes bifurcate intramacularly, and small-diameter, U-type nerve fibers have long, unmyelinated preterminal axons and up to three branches. Preterminals of these nerve fibers display ultrastructural heterogeneity that is correlated with labeling patterns for sodium channels and/or associated polyanionic sites. They have a nodelike ultrastructure and label heavily from near the heminode to the base of the macula. Their intramacular branches, less organized ultrastructurally, label only slightly. Results indicate that vestibular nerve fibers have one impulse initiation zone, located near the heminode, that varies in length according to nerve fiber type. Structural heterogeneity may favor impulse conduction in the central direction, and length of the impulse initiation zone could influence nerve discharge patterns.

Acoustic Maculae

Evaluation of rodent sperm, vaginal cytology, and reproductive organ weight data from National Toxicology Program 13-week studies.

Sperm morphology and vaginal cytology examinations (SMVCEs), which include evaluations of motility, concentration and head morphology of sperm from the cauda epididymis, and male reproductive organ weight data, were developed by the National Toxicology Program as a screening system for reproductive toxicants. An analysis was conducted of SMVCE studies carried out at the end of fifty 13-week studies (25 for rats, 25 for mice) over a 3-year period. Statistically significant changes in these studies were summarized, as were control data for each male endpoint (mean, SD, 95% confidence limits around the mean, median, and statistical power). Reproductive organ weights (testis, epididymis, cauda epididymis) and sperm motility were the most statistically powerful endpoints evaluated; sperm head morphology may also be a sensitive endpoint for detecting reproductive toxicants. For 24 chemicals tested in both rats and mice, the concordance of results [i.e., no adverse effect in either species, or at least one SMVCE endpoint (not necessarily the same one) adversely affected in both species] was 58%. These data suggest that detection of potential reproductive toxicants might be best when both species are used. Types of sperm head abnormalities and their relative proportion of the total did not differ among control and treatment groups. Estrous cycle data were obtained in the final week of forty-six 13-week studies (23 for mice, 23 for rats). Only 3 chemicals caused an increase in mean cycle length compared with the control group. More data from breeding studies in which female estrous cycle length is measured are needed to assess fully the association of cycle length with reproductive outcome; stages of the estrous cycle are so variable that they may not be useful in assessing potential toxicity. Interlaboratory variability in SMVCE values for many endpoints was documented. Very few of the chemicals that form the basis of this report have been evaluated in definitive reproductive toxicology protocols; a companion paper compares changes in SMVCE endpoints with the outcome of continuous breeding reproduction studies.

Animals

Otoconia as test masses in biological accelerometers: what can we learn about their formation from evolutionary studies and from work in microgravity?

This paper reviews previous findings and introduces new material about otolith end organs that help us to understand their functioning and development. In particular, we consider the end organs as biological accelerometers. The otoconia are dealt with as test masses whose substructure and evolutionary trend toward calcite may prove significant in understanding formation requirements. Space-flight helps illuminate the influence of gravity, while right-left asymmetry is suggested by study of certain rat strains.

Aging

Effects of ethylene glycol monomethyl ether (EGME) on mating performance and epididymal sperm parameters in F344 rats.

Previous histologic studies on the effects of EGME identified dividing spermatocytes as a primary target cell type in the testis. The following studies were undertaken to assess possible effects of EGME on late-stage and epididymal spermatids, and spermatogonia. Adult male F344 rats (n = 20/group) of proven fertility were dosed po with 0, 50, 100, or 200 mg EGME/kg/day for 5 days. Each male was then mated with two females/week for 8 weeks. Females were sacrificed ca. 2 weeks after removal from the male, and number of live and dead fetuses, resorption sites, and corpora lutea were noted. Additional males were treated similarly, sacrificed at weekly intervals, and measures of epididymal sperm count, motility, and morphology were made. The fertility of males treated with 200 mg EGME/kg declined at Week 4, and remained low for the rest of the study. There was a modest but significant increase in the number of resorption sites at Weeks 5 and 6 in the high dose group. There was a decrease in the number of litters sired at Week 5 after dosing in the 100-mg EGME/kg group. There were time- and dose-related decreases in sperm concentration and motility, primarily in the 100- and 200-mg/kg groups, as well as concurrent elevations in the number of abnormal sperm forms in the epididymis. These studies show that EGME is a very weak inducer of dominant-lethal mutations, and produces previously undescribed effects on late-stage spermatids and spermatogonia.

Animals

The recovery of the testis over 8 weeks after short-term dosing with ethylene glycol monomethyl ether: histology, cell-specific enzymes, and rete testis fluid protein.

Ethylene glycol monomethyl ether (EGME) has been found to affect meiotic spermatocytes, spermatids, other stages of spermatocytes, and spermatogonia, depending on the dose used. These studies, which examine testicular recovery from EGME treatment, analyzed tissues from rats treated for 5 days with 0, 50, 100, or 200 mg EGME/kg/day and sacrificed at eight subsequent weekly intervals; some epididymal sperm parameters of these animals have been described. Histologically, the testes of the low-dose group showed very mild changes, while the 100- and 200-mg/kg groups showed widespread damage and cell death which recovered somewhat during the course of the study. There was no treatment-related effect on seminal vesicle or prostate weights. Rete testis fluid protein levels were changed only in the high-dose group, when protein levels rose to a maximum of sixfold the control values at Week 4; by Week 6, there was no difference between groups. Changes in cell-specific enzyme activities were dose dependent and generally mirrored changes in the number of germ cells in the testis.

Acid Phosphatase

Changes in distribution of lung perfusion and ventilation at rest and during maximal exercise.

A new method for evaluation of changes in the distribution of pulmonary perfusion and ventilation during exercise was applied to normal male volunteers. Ventilation and perfusion scans were done with the subjects seated on a bicycle ergometer. The resting studies utilized krypton 81 (81mKr) for ventilation and technetium 99m (99mTc) macroaggregate albumin intravenously for perfusion. Exercise studies were done when 80 percent of maximum predicted heart rate was maintained for five minutes and utilized 81mKr for ventilation and a tenfold dose of 99mTc for perfusion. Higher dose of 99mTc would minimize the effect of radioactivity left over from the resting study. This method allowed us to assess changes in ventilation and perfusion in normal subjects induced by exercise, but may also be applicable in a variety of cardiopulmonary conditions that affect pulmonary ventilation and perfusion or both.

Adult

Anatomic evidence for peripheral neural processing in mammalian graviceptors.

Ultrastructural study of utricular and saccular maculas demonstrates that their innervation patterns are complex. There is a clustering of type I and type II hair cells based upon a sharing of afferents, a system of efferent-type beaded fibers that is of intramacular (mostly calyceal) origin, and a plexus-like arrangement of afferents and efferents at many sites in the neuroepithelium. Results suggest that information concerning linear acceleration is processed peripherally, beginning at the hair cell level, before being sent to the central nervous system. The findings may supply a structural basis for peripheral adaptation to a constant stimulus, and for lateral inhibition to improve signal relative to noise.

Acoustic Maculae

Calcium ion uptake and exchange in otoconia.

Calcium ion uptake into otoconia and bone mineral of the young adult rat was studied by use of 45Ca and liquid scintillation spectrometry. Results showed that saccular and utricular otoconia take up 45Ca in a time course generally comparable to bone but on a much lower scale. Saccular otoconia showed greater uptake than utricular. The results are interpreted to indicate the dynamic nature of saccular and utricular otoconia and their possible importance in preserving ionic homeostasis of the inferior and superior parts of the labyrinth, respectively.

Animals