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Biomedical subjects

R D McKay

Publications and source records attributed to R D McKay.

89 records · Page 5Linked to original sources

Axonal projections of mechanosensory neurons in the connectives and peripheral nerves of the leech, Haemopis marmorata.

The axonal projections of the seven mechanosensory neurons in the connectives and peripheral nerves were examined by horseradish peroxidase (HRP) injections. In the connective the closely functionally related mechanosensory neurons travel in two bilaterally symmetrical regions, which comprise less than 10% of the connective's cross-sectional area. This grouping may reflect the similar functional properties and synaptic connections of the cells. Serial sections through the neuropil-connective junction zone showed that the organization of the axons is independent of glial fasciculation. Fascicles are not rigid structures; they were found to part and fuse in a seemingly random manner. The glial cell seems therefore to have only a supportive structural function and not to play any role in axonal guidance or to define any specific nerve fascicles in the leech. The projections of the mechanosensory cells in the peripheral roots were not as stereotyped as in the connective. However, examination of the branching of the medial and lateral P cells in the posterior root showed that the roots are highly structured and that some axons may be confined to tracts which have specific positions related to the branching of the root. The possible role of the P cells in pioneering these tracts is discussed.

Animals↗

Distribution and morphology of nociceptive cells in the CNS of three species of leeches.

The present study describes the segmental variation in the distribution and morphology of nociceptive neurons (N cells) in the central nervous system of the leech. N cells of midbody ganglia can be segregated into lateral and medial types. We show that monoclonal antibodies specific for N cells can distinguish between the two populations. The monoclonal antibodies were used to map the complete distribution of the cells along the nervous cord. There are two pairs of the medial and lateral nociceptive neurons in the midbody ganglia, one pair of the medial type in the sex ganglia (5 and 6), and a pair of the lateral type in ganglia 20 and 21. The caudal brain is without nociceptive neurons. This distribution was confirmed by electrophysiological means. The morphology of N cells in different parts of the nervous system was investigated by intracellular horseradish peroxidase (HRP) injections. In the terminal segmental ganglia the N cells showed extensive arborizations in the head and tail brains and, contrary to N cells in the midbody ganglia, their arborizations spanned more than three segments. N cells are absent in the tail brain, but the N cells of ganglia 20 and 21 were shown to innervate the entire caudal region. The basic morphology of all N-cell homologues was found to be very similar for three leech species. In the sex ganglia the pair of N-cell homologues were examined in Haemopis, Hirudo, and Macrobdella. The results showed a progressive modification in the three species of the cell's morphology, peripheral projections, and physiological responses, possibly correlated with the evolution and complexity of the sexual organs. HRP injections and monoclonal antibody staining revealed that a common feature of N-cell homologues is the presence of processes that tightly surround the cell soma of other cells. This suggests that N cells may have other functional properties in addition to being primary sensory neurons.

Animals↗

Factors and their influence on regional cerebral blood flow during nonpulsatile cardiopulmonary bypass.

In this study we examined the relationship of regional cerebral blood flow (CBF) to mean arterial pressure, systemic blood flow, partial pressure of arterial carbon dioxide (PaCO2), nasopharyngeal temperature, and hemoglobin during hypothermic nonpulsatile cardiopulmonary bypass (CPB). Regional CBF was determined by clearance of xenon 133 in 67 patients undergoing coronary bypass grafting procedures. There was a significant decrease in regional CBF (55% decrease) during CPB, with nasopharyngeal temperature and PaCO2 being the only two significant factors (p less than 0.05). In a subgroup of 10 patients, variation of pump flow between 1.0 and 2.0 L/min/m2 did not significantly affect regional CBF. We conclude that cerebral autoregulation is retained during hypothermic CPB. Under the usual conditions of CPB, variations in flow and pressure are not associated with important physiological or detrimental clinical affects.

Adult↗

Correlation of cerebral blood flow and EEG during carotid occlusion for endarterectomy (without shunting) and neurologic outcome.

One hundred twenty-nine consecutive carotid endarterectomies performed for atherosclerotic ulcerative stenosis without the use of intraoperative shunting were analyzed prospectively in an effort to determine the significance of intraoperative ischemia. Intraoperative EEG and regional cerebral blood flow measurements were used to monitor these patients. Ten of the patients were excluded because of inadequate data, but none of these 10 patients experienced a complication. Factors analyzed included preoperative risk assessment according to the Mayo Clinic system of Sundt et al., intraoperative regional cerebral blood flow measurements, and intraoperative EEG changes. The overall mortality rate was 2.5%, the major morbidity rate was 2.5%, the minor morbidity rate was 1.7%, and the rate of transient neurologic dysfunction was 1.7%. The patients' preoperative state as determined according to the Mayo Clinic system of Sundt et al. was more useful in identifying patients at risk than was intraoperative EEG and regional cerebral blood flow monitoring.

Anesthesia, General↗

Surface molecules identify groups of growing axons.

Studies on vertebrate and invertebrate species have established that, during development, axons have the ability to choose particular paths over others. The chemical basis of this pathfinding is not clear but biochemical differences between neurons have long been postulated to account for the specificity of neuronal connections. Such subtle molecular differences between different cells in a single tissue are difficult to study with standard biochemical techniques but hybridoma technology has offered a potential solution to this type of problem. This technique has made possible the production of monoclonal antibodies for identifying and characterizing a family of glycoproteins which are expressed on the surface of specific axon bundles during the development of the leech nervous system. The results show that groups of growing axons do indeed carry chemically distinct surface molecules.

Animals↗

A surface antigen expressed by a subset of neurons in the vertebrate central nervous system.

Many hypotheses for the specificity of connections in the nervous system postulate the presence of surface chemical differences between neurons. Hybridoma technology offers a potential route to identify such surface antigenic differences between neurons. Monoclonal antibody Cat-301 was one of a panel of antibodies generated by immunizing mice with homogenized adult cat spinal cord. At the light microscopic level, Cat-301 recognizes a subset of neurons in many areas of the vertebrate central nervous system. This report shows at the ultrastructural level that Cat-301 binds to a surface antigen on neurons in the intact vertebrate central nervous system. Cat-301-positive neurons carry the antigen on cell bodies and proximal dendrites but not on axons. Using secondary antibody labeled with horseradish peroxidase, we show that antibody binding sites are present along the surfaces of neurons and extend around presynaptic profiles but are excluded from the synaptic cleft. The distribution of the Cat-301 antigen at central synapses is similar to that described for some components of the extracellular matrix of the neuromuscular junction. This study demonstrates that a specific surface antigen is found on a subset of neurons and suggests that other surface markers may be present on other subsets of mammalian central nervous system neurons. Antibodies against this antigen and other surface antigens may allow insight into the mechanisms involved in the formation and maintenance of synaptic connections in the central nervous system.

Animals↗

Monoclonal antibodies distinguish antigenically discrete neuronal types in the vertebrate central nervous system.

Eight hundred hybridoma lines were generated from mice immunized with the fixed gray matter of cat spinal cord. Of these lines, 47 were positive when screened immunohistochemically against sections of the cat spinal cord. Twenty-nine lines secreted antibodies that bound to neuronal antigens. Of these, 16 bound to axons only, 8 bound to axons and cell bodies, and 5 bound to cell bodies only. Eighteen lines secreted antibodies that bound to glial cells. Five lines that secreted antibodies that intensely stained spinal cord sections were cloned and screened against other parts of the central nervous system. Each of these five antibodies bound to specific subsets of neurons. For example, in the spinal cord, one antibody (Cat-301) recognized a surface determinant on the dendrites and cell bodies of neurons that, in morphology and location, resemble long-distance projection neurons. A second antibody (Cat-201) recognized an antigen in axons and in the cytoplasm of neuronal cell bodies that may be a subset of those recognized by Cat-301. A third antibody (Cat-101) recognized only axons. The subcellular localization of the antigen recognized by each antibody is the same in all areas of the central nervous system we have examined. The fact that each of the antibodies described here has a restricted distribution in the central nervous system shows that there is a high degree of molecular diversity among vertebrate neurons and that hybridoma technology can be used to explore this diversity. This class of reagents should be a useful addition to the many established techniques for studying the organization of the vertebrate central nervous system.

Antibodies, Monoclonal↗

Evolution of a human Y chromosome-specific repeated sequence.

The structure and evolution of a repetitive sequence on the human Y chromosome has been studied by restriction enzyme analysis of both total DNA and the isolated sequence. The sequence is shown to cross-hybridize to sequences in female DNA forming unstable duplexes. Mouse/human cell hybrids have been used to investigate the pattern of sequence homology on the X chromosome and some autosomes. We conclude that this sequence is related to human satellite III, but shows considerable differences in structure.

Base Sequence↗

The identification of a repeated DNA sequence involved in the karyotype polymorphism of the human Y chromosome.

We show that individual men are polymorphic for the amount of two different repeated DNA sequences. The amount of one of these sequences is proportional to the length of the brightly fluorescent heterochromatin on the Y chromosome. There are no detectable alterations in sequence between polymorphic individuals. Female DNA contains sequences complementary to those found on the Y, but at a much reduced level.

Base Sequence↗

Internal carotid artery stump pressure and cerebral blood flow during carotid endarterectomy: modification by halothane, enflurane, and innovar.

Carotid endarterectomy requires temporary surgical occlusion of the involved carotid artery. During occlusion, the minimally acceptable (critical) internal carotid artery stump pressure is reported to be 50 torr, whereas for regional cerebral blood flow (rCBF), a critical range is reported to be 18-24 ml/100 g/min. During 90 carotid endarterectomies, rCBF and stump pressure were measured and the EEG continuously monitored. A positive correlation between rCBF and stump pressure (i.e., when both were either above or below their respective critical values) was observed in only 58 per cent of the cases. In 28 per cent stump pressures of less than 50 torr were observed despite rCBF's above 24 ml/100 g/min and normal EEG's. In 8 per cent stump pressures were more than 50 torr but rCBF's were less than 18 ml/100 g/min and EEG changes of ischemia were commonly observed. In the remaining 6 per cent rCBF's were marginal (18-24 ml/100 g/min) while stump pressures were more than 50 torr and EEG changes were not observed. The relationship between stump pressure and rCBF was influenced by the anesthetic. In the absence of transient ischemia during occlusion (that is, rCBF greater than 18 ml/100 g/min), halothane and enflurane anesthesia were associated with significantly higher rCBF's and lower stump pressures than was neuroleptanesthesia. Pre-occlusion and post-occlusion rCBF measurements also demonstrated cerebral vasodilation by halothane and enflurane (halothane greater than enflurane) and vasoconstriction by neuroleptanesthesia. It is concluded that stump pressure is an unreliable index of CBF during carotid occlusion and that its relationship to CBF is considerably influenced by the anesthetic.

Blood Flow Velocity↗