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Biomedical subjects

M E Anderson

Publications and source records attributed to M E Anderson.

At least 163 records · Page 9Linked to original sources

An autoradiographic study of efferent connections of the globus pallidus in Macaca mulatta.

Radioactive amino acids were injected into restricted regions of the globus pallidus of rhesus macaques to allow identification of the organization and courses of efferent pallidal projections. The previously identified projection of the internal pallidal segment (GPi) to ventral thalamic nuclei showed a topographic organization, with the predominant projection from ventral GPi being to medial and caudal ventralis anterior (VA) and lateralis (VL) and from dorsal GPi to lateral and rostral VA and VL. Pallidal efferent fibers also extended caudally and dorsally into pars caudalis of VL, but they spared the portion of pars oralis of VL shown by others to receive input from the cerebellum. In addition to centromedian labeling in all animals, the parafascicular nucleus was also labeled when isotope was injected into dorsal GPi. The medial route from GPi to the midbrain tegmentum was more substantial than has been shown before, and along this route there was an indication that some fibers terminated in the prerubral region. The projection to the pedunculopontine nucleus was extensive, and fibers continued caudally into the parabrachial nuclei. Pallidal projections to the thalamus seem to be topographically organized but spare thalamic regions that interact with area 4. Caudally directed efferent fibers follow multiple routes and extend more caudally than to the pedunculopontine nuclei.

Animals↗

Interconversion of leukotrienes catalyzed by purified gamma-glutamyl transpeptidase: concomitant formation of leukotriene D4 and gamma-glutamyl amino acids.

The reversible conversion of leukotriene C4 to leukotriene D4 and of the latter to leukotriene E4 were studied with highly purified homogeneous preparations of gamma-glutamyl transpeptidase, dipeptidase, and aminopeptidase M. The conversion of leukotriene C4 to leukotriene D4, catalyzed by gamma-glutamyl transpeptidase, is significantly more rapid when carried out in the presence of an amino acid mixture a closely approximating that found in blood plasma and is accompanied by gamma-glutamyl amino acid formation. Because gamma-glutamyl transpeptidase is bound to the external surface of cell membranes and thus is readily accessible to plasma amino acids, it appears that conversion of leukotriene C4 to leukotriene D4 under physiological conditions is coupled with the formation of gamma-glutamyl amino acids. The apparent Km value for leukotriene C4 in this reaction is about 6 X 10(-6) M, a value close to that found for glutathione. Conversion of leukotriene D4 to leukotriene C4 is effectively catalyzed by gamma-glutamyl transpeptidase in the presence of relatively low concentrations of glutathione. The conversion of leukotriene D4 to leukotriene E4 is catalyzed much more rapidly by renal dipeptidase than by renal aminopeptidase M. Incubation of leukotriene E4 with gamma-glutamyl transpeptidase and glutathione leads to formation of a compound with the properties of gamma-glutamyl leukotriene E4; this reaction is analogous to that shown previously in which gamma-glutamyl cystine is formed by transpeptidation between glutathione and cystine.

Aminopeptidases↗

Urinary tract infections due to Staphylococcus saprophyticus biotype 3.

Staphylococcus saprophyticus biotype 3 (Micrococcus subgroup 3 or M3) has usually been shown to be the second commonset cause of urinary tract infections in European women who are not in hospital. It generally causes pyuria and symptoms as severe as those caused by Escherichia coli. Unlike S. epidermidis it is seldom found as a contaminant in midstream urine specimens, and almost exclusively infects women in their reproductive years. However, S. saprophyticus is seldom differentiated from S. epidermidis in Canadian clinical laboratories. Urinary isolates of S. saprophyticus were presumptively differentiated from other coagulase-negative Micrococcaceae by their resistance to novobiocin as demonstrated by a simple disc susceptibility test that misidentified the infecting organism in only 3.4% of specimens. These novobiocin-resistant, coagulase-negative organisms caused similar proportions of the urinary tract infections in young women in York, England and Vancouver -- 6.6% and 6.9% respectively. In York these organisms were associated with significantly greater pyuria than novobiocin-sensitive organisms or bile-tolerant streptococci but not S. aureus or Enterobacteriaceae. In both communities novobiocin-sensitive, coagulase-negative Micrococcaceae were appreciably more resistant to penicillin than novobiocin-resistant organisms. Thus, differentiating S. saprophyticus from novobiocin-sensitive, coagulase-negative organisms provides information that is clinically useful, particularly for primary care practitioners working in the community or in outpatient clinics.

Adult↗

Effect of imidazole on renal function in unilateral ureteral-obstructed rat kidneys.

Imidazole has been proposed to reverse renal vasoconstriction following unilateral obstruction, presumably through blockade of thromboxane A2 (TXA2) synthesis. We examined this hypothesis in rats subjected to unilateral ureteral obstruction for 24 h by 1) performing renal function studies before and during imidazole infusion, and 2) measuring TXB2 and prostaglandin E2 (PGE2) in urine collected before and during imidazole infusion and the profile of products generated by metabolism of arachidonic acid with renal microsomes in vitro. Imidazole infusion was associated with only a bicarbonaturia in the postobstructed kidney; in contrast, clearance of PAH and inulin, fractional sodium excretion, and bicarbonate excretion were all increased in the contralateral kidney. In the postobstructed and contralateral kidneys, TXB2 excretion was diminished and PGE2 excretion was variable not only following imidazole infusion but after saline infusion as well. The profile of products generated by renal microsomal metabolism of arachidonic acid was similar among obstructed, contralateral, and normal kidneys. These results do not support the proposal that TXA2 is the mediator of renal vasoconstriction following unilateral ureteral obstruction.

Animals↗

Interaction of L- and D-3-amino-1-chloro-2-pentanone with gamma-glutamylcysteine synthetase.

The optical isomers of 3-amino-1-chloro-2-pentanone, which are the alpha-chloroketone analogs of L- and D-alpha-aminobutyrate, were synthesized and found to be highly potent irreversible inactivators of gamma-glutamylcysteine synthetase. These chloroketones are 20 to 30 times more active than L-2-amino-4-oxo-5-chlorpentanoate. L- and D-Glutamate, in the presence of Mg2+ or Mn2+, protect the enzyme against inactivation. The enzyme is almost completely inhibited by cystamine under conditions in which 0.5 mol of this compound is bound/mol of enzyme. Treatment of the enzyme with cystamne, which produces inhibition that is reversible by dithiothreitol, prevents the interaction of the new chloroketones, L-2-amino-4-oxo-5-chloropentanoate and methionine sulfoximine with the enzyme. The findings suggest that a sulfhydryl group at the active site interacts with the chloroketones and with cystamine and that the chloroketone inhibitors and cystamine bind to the enzyme as glutamine analogs. The data also suggest that a gamma-glutamyl-S-enzyme intermediate may be formed in the reaction catalyzed by this enzyme.

Animals↗

Dynamic state of glutathione in blood plasma.

Recent studies have shown that there is an interorgan cycle of glutathione metabolism in which glutathione is translocated from certain cells into the blood plasma, and that plasma glutathione is utilized by cells that have gamma-glutamyl transpeptidase. The present studies indicate that there is a significant intravascular phase of glutathione metabolism. The level of total glutathione (GSH + GSSG) in rat blood plasma was found to be 22 to 27 microM GSH equivalents, as determined by the glutathione reductase recycling method. About 85% of the total is in the form of GSH. These findings contrast with previous reports of total levels of 3 to 6 microM and 50 to 75% GSSG. We found that plasma allowed to stand at 23 degrees C for 30 to 60 min has total glutathione levels of 4 to 7 microM, most (95%) of which is GSSG; after treatment of this plasma (following deproteinization) with KBH4, levels of 21 to 24 microM were found. GSH disappears rapidly from plasma, whereas GSSG disappears very slowly. gamma-Glutamyl transpeptidase does not account for the loss of plasma GSH, nor does binding to proteins account for more than a small fraction of the GSH that disappears. Most of the GSH that disappears can be found in the deproteinized samples after treatment with KBH4. The findings are in accord with the view that glutathione is translocated to plasma in the form of GSH and that such GSH constitutes the major source of plasma thiol. The intravascular phase of GSH metabolism seems to involve reduction of disulfide bonds of plasma constituents and mobilization of compounds bound by disulfide linkage to plasma proteins to form GSSG and low molecular weight derivatives of glutathione such as disulfides.

Animals↗

A horseradish peroxidase study of afferent connections of the globus pallidus in Macaca mulatta.

The high tonic discharge rates of globus pallidus neurons in awake monkeys suggest that these neurons may receive some potent excitatory input. Because most current electrophysiological evidence suggests that the major described pallidal afferent systems from the neostriatum are primarily inhibitory, we used retrograde transport of horseradish peroxidase (HRP) to identify possible additional sources of pallidal afferent fibers. The appropriate location was determined before HRP injection by mapping the characteristic high frequency discharge of single pallidal units in awake animals. In animals with injections confined to the internal pallidal segment, retrograde label was seen in neurons of the pedunculopontine nucleus, dorsal raphe nucleus, substantia nigra, caudate, putamen, subthalamic nucleus, parafascicular nucleus, zona incerta, medial and lateral subthalamic tegmentum, parabrachial nuclei, and locus coeruleus. An injection involving the external pallidal segment and the putamen as well resulted in additional labeling of cells in centromedian nucleus, pulvinar, and the ventromedial thalamus.

Afferent Pathways↗

Axonal branching patterns and location of nigrothalamic and nigrocollicular neurons in the cat.

1. Antidromic activation from the thalamus and the superior colliculus was used to identify the axonal projections of neurons in the substantia nigra. 2. Up to 43% of the nigral neurons studied in individual animals had branching axons that could be activated antidromically from both the ipsilateral ventromedial thalamus and the ipsilateral superior colliculus. 3. For several neurons, the conduction time spent in the unbranched axonal segment could be calculated using measurable collision and antidromic latency times. Time in the unbranched segment was less than 20% of the antidromic latency for most neurons studied. 4. Latencies for antidromic activation from the thalamus were measured and would be appropriate if these axons were to mediate the monosynaptic nigrothalamic inhibition reported earlier. 5. Stimulation of the caudate nucleus produced inhibition of spontaneous activity of both collicular- and thalamic-projecting neurons.

Animals↗

Eye and head movements in reading-disabled and normal children.

Coordination of eye and head movements on nonreading tasks was investigated in 16 reading-disabled and 18 normal children aged 6 to 11 years. Types of eye movements are described and mechanisms controlling eye and head movement are reviewed. Significant differences were found between the two groups in sequencing of eye and head movements that were made in response to the appearance of visual stimuli at unexpected times and positions. Some reading-disabled children also were found to require more eye movements to achieve fixation on targets at known positions. It is suggested that the vestibular system may be implicated as a factor in the results obtained from the reading-disabled children and that the atypical eye-head movement patterns observed may did in stabilizing their visual world.

Adult↗

Quadriplegia associated with narrow cervical canal, ligamentous calcification and ankylosing hyperostosis.

The occurrence of three pathological entities of the cervical spine--ankylosing hyperostosis, calcification of the posterior longitudinal ligament, congenitally narrowed cervical canal--in a single patient is reported. This combination of pathology led to a severely narrowed cervical canal and a spine with abnormal mobility at non-fused levels. Minor trauma to the patient resulted in permanent quadriplegia.

Ankylosis↗

Paraformaldehyde-induced fluorescence as a histochemical test for 5-hydroxytryptamine in the epididymis of the opossum.

Epididymides of four opossums were tested histochemically for the presence of 5-hydroxytryptamine (5-HT). In addition, testes and epididymides of two opossums were analysed biochemically for the same substance. Biochemical analysis revealed a high concentration of 5-HT in the epididymis, while the amount in the testis proved to be insignificant. Fluorescence microscopy gave positive results in the apical portion of the epithelium. There was also fluorescence in the connective tissue in general, in mast cells, and in a thick subepithelial band in particular. Following treatment with 2% sodium borohydride in 1,2-propanediol for 15 minutes, the fluorescence of mast cells was removed, while there was a slight reduction in epithelial fluorescence and that in the subepithelial band and other connective tissue. The subepithelial band stained metachromatically with azure B, and this staining characteristic was removed by treatment with RNAse. Feulgen reaction revealed elongate nuclei in the band. It would seem that the 5-HT is located in both the mast cells and the epithelium. It seemed to be also present in the subepithelial band, but because of strong autofluorescence it is difficult to demonstrate. At the present time the function of 5-HT in the opossum epididymis is unknown, and is under further investigation.

Animals↗

Discharge patterns of basal ganglia neurons during active maintenance of postural stability and adjustment to chair tilt.

Neurons in the putamen and globus pallidus were studied in awake monkeys making active postural adjustments during static and dynamic chair tilt. When the chair was held horizontal and the monkey actively maintained a restricted head position, neurons had tonic firing rats similar to those described previously, with low frequency patterns in the putamen and low frequency-burst or intermediate (IFD) to high frequency (HFD) tonic patterns in neurons in the pallidal segments. Over half of the neurons with IFD or HFD discharge rates and a smaller proportion of those with slow discharge rates showed changes in firing that were temporally correlated with chair tilt. Phase shifts of firing frequency relative to sinusoidally vaired chair position varied in units with different tonic discharge frequencies. Maximum and minimum discharge rates in IFD neurons occurred near maximum chair velocities, whereas the phase shift decreased in HFD neurons, which had higher discharge rates during the horizontal chair position. Neurons with changes in discharge during chair tilt were found in all portions of the putamen and globus pallidus studied.

Action Potentials↗

Segmental reflex inputs to motoneurons innervating dorsal neck musculature in the cat.

The responses to stimulation of upper cervical muscle and cutaneous afferents were studied in motoneurons innervating splenius, complexus, and biventer cervicis dorsal neck muscles of cats. Motoneurons innervating complexus and biventer cervicis fibers, which are in the deeper, longitudinally oriented muscles, were monosynaptically excited by ipsilateral Group I afferents from each of these muscles, but they did not receive significant input from splenius Group I afferents. Likewise, splenius motoneurons were not monosynaptically excited by ipsilateral afferents from complexus anf biventer cervicis. Stimulation of ipsilateral cutaneous afferents produced predominant excitation in splenius motoneurons, predominant inhibition in biventer cervicis motoneurons, and inhibition or mixed responses in complexus motoneurons. None of the neck motoneurons studied showed postsynaptic potentials following single or multiple shock stimulation of contralateral muscle nerves at stimulus intensities expected to excite exclusively Group I afferents. Higher intensity stimulation of contralateral muscle afferents, as well as fibers in the greater auricular nerves, produced predominant inhibition in all three neck motoneuron pools. Segmentally-excited afferents to neck motoneurons, like those from supraspinal systems, appear to evoke different patterns of synaptic responses in splenius motoneurons than they do in motoneurons innervating fibers in the deeper, longitudinally oriented complexus and biventer cervicis muscles.

Animals↗

Diet and cancer.

Differences in food intake patterns are positively correlated with differences in the incidence of various cancers in world populations. It is postulated here that dietary factors play a vital role in the genesis of several major neoplasms, specifically gastric and colon carcinomas. In addition to the food consumed, such variables as total caloric intake, nutrtional excess or deficit, exposure to carcinogens and consumption of alcohol also increase the risk of cancer. Through recognition of these factors and subsequent long-term manipulation of diet, it should be possible to reduce cancer morbidity and mortality.

Alcohol Drinking↗