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K A Martin

Publications and source records attributed to K A Martin.

At least 109 records · Page 6Linked to original sources
PubMed1991

Precursors of alpha-inhibin modulate follicle-stimulating hormone receptor binding and biological activity.

Although several forms of monomeric alpha-inhibin have been isolated from follicular fluid, no biological function has yet been ascribed to these posttranslationally processed forms of the alpha-subunit precursor protein. Moreover, previous studies of a FSH receptor binding competitor (FRBC) isolated and characterized from porcine follicular fluid (pFF) suggested certain biochemical similarities between this protein and alpha-inhibin precursors. We, therefore, investigated the hypothesis that alpha-inhibin and/or its precursors might represent autocrine and/or paracrine modulators of FSH action in the ovary, accounting for some of this FRBC activity and thereby exerting some degree of regulation over follicular maturation. Three separate sources of alpha-inhibin proteins were investigated for FRBC activity, including pFF, human FF (hFF), and a 293 cell line into which the full-length human alpha-inhibin cDNA had been stably transfected. Conditioned medium from these transfected cells contained several forms of alpha-inhibin precursors as well as mature alpha-inhibin, but no beta-subunit or intact inhibin. alpha-Inhibin proteins from all three sources, purified by a variety of methods, including immunoaffinity chromatography on an anti-alpha-inhibin column, inhibited FSH binding to both natural tissue FSH receptors as well as recombinant rat FSH receptors expressed in 293 cells. Furthermore, dimeric inhibin and activin, medium from untransfected 293 cells, and non-alpha-inhibin-containing purification fractions were inactive in either assay. In addition, purified recombinant alpha-inhibin proteins were partial in vitro FSH antagonists in a bioassay in which cAMP generation from 293 cells expressing the recombinant FSH receptor is used as an index of FSH biological activity. These same fractions of hFF containing FRBC activity did not bind to LH receptors, thereby demonstrating receptor specificity for this activity. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting with alpha-inhibin or FRBC antisera, a 57,000 mol wt protein was identified in FRBC-active fractions from all three sources, suggesting that the active moiety was the full-length alpha-inhibin precursor protein or a large mol wt fragment, but not mature alpha-inhibin. Lastly, all FRBC activity from all three sources was extracted by an alpha-inhibin immunoaffinity column and was recoverable upon elution. These results demonstrate that proteins derived from the alpha-inhibin precursor modulate FSH binding to its receptor as well as its biological activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Prevalence of hearing impairment among university students.

The prevalence of hearing impairment in university students was determined from a 6-year, pure-tone hearing screening conducted at 20 dB HL for the octave frequencies from 500 to 4000 Hz. Of the 18,424 students tested, 1.2 percent failed the screening. The ratio of unilateral to bilateral hearing impairment was found to be approximately 1:1. Sensorineural hearing loss was four times more prevalent than conductive hearing loss in this population and significant hearing loss at 4000 Hz was evident in 61 percent of the males who failed the screen.

Female↗
PubMed1991

Effects of monocular visual deprivation on geniculocortical innervation of area 18 in cat.

The effects of long-term monocular visual deprivation (MD) on the structure of the terminal arborizations of individual Y-type geniculocortical axons was studied in the cat's cortical area 18. Physiologically classified axons were filled with HRP by intracellular injection, and the three-dimensional distribution of the axons' terminal arborizations was quantified. Individual boutons observed at the light microscope (LM) level were verified as sites of synaptic contact by correlated light and electron microscopy (EM). Single boutons were serially sectioned and reconstructed for subsequent three-dimensional analysis. The arborizations of 17 Y-axons [6 normal (N), 6 nondeprived (ND), and 5 deprived (D)] were analyzed at the LM level, and 372 boutons (104 N, 129 ND, and 139 D) were fully reconstructed from serial sections for analysis at the EM level. MD leads to an expansion in the size of ND arborizations and a variable reduction in the size of the D arbors, which also have a higher bouton density than ND arborizations. ND axons form ectopic synapses, contacting proportionally more dendritic shafts than N or D boutons, and form more synapses per bouton, on average, than either N or D boutons. Compared to ND and N boutons, boutons of D axons are smaller, have fewer mitochondria, generally form synapses on a single target (usually dendritic spines), and occasionally make no synaptic contacts. The structural changes in the extent of individual axon arborizations may be the basis for change in ocular dominance column size with MD. However, the higher bouton density and variable effect on the extent of D axon arborization size suggest that considerable geniculocortical innervation from the deprived eye remains intact. The change in target preference for ND axons suggests that instead of a direct competition for postsynaptic sites by the developing geniculocortical axons innervated by the two retinas, the ND axon arborizations expand to invade synaptic space not normally occupied in such high proportion in the normal cortex. The severe changes in individual boutons following MD indicate that arborization size alone is not the only structural substrate underlying the altered responses of cortical neurons; changes in synaptic distribution onto target neurons may also play a role.

Animals↗
PubMed1990

Specificity switching of the P1 plasmid centromere-like site.

The P1 plasmid partition site acts like a centromere, promoting accurate segregation of copies to daughter cells. A 34 bp segment is essential for partition and binds the plasmid ParB protein. Additional sequences act as specificity elements that direct the choice of copies for partition. They include a second ParB binding site and a site for the host integration host factor protein. Sites lacking one or more of these additional elements are switched to a different specificity. Defined mutants were scored for partition specificity and protein binding. The results suggest that the wild-type site is folded in a specific DNA-protein complex. Disruption of the complex leads to an open configuration which, while still active in partition, has altered recognition specificity.

Base Sequence↗
PubMed1990

Analysis of associative learning in the terrestrial mollusc Limax maximus. II. Appetitive learning.

The odor and taste processing systems of the terrestrial mollusc Limax maximus have been shown capable of a number of complex computations. Most of the complex higher-order features of Limax learning have been demonstrated using differential aversive conditioning. The present experiments probe the appetitive learning ability of Limax. In the first experiment a differential appetitive classical conditioning procedure was used. An aversive CS+ odor was paired with an attractive taste while a CS- odor was explicitly unpaired with the attractive taste. This appetitive conditioning procedure dramatically increased the preference for the CS+ odor. Further experiments determined the time course of acquisition, the effect of an extinction procedure and long-term retention of the appetitive conditioning. Now that Limax has been shown capable of appetitive conditioning, the neural network simulation of Limax learning, called LIMAX, can be examined for its ability to display appetitive conditioning.

Animals↗
PubMed1989

Arborisation pattern and postsynaptic targets of physiologically identified thalamocortical afferents in striate cortex of the macaque monkey.

The monosynaptic targets of different functional types of geniculocortical axons were compared in the primary visual cortex of monkeys. Single thalamocortical axons were recorded extracellularly in the white matter by using horseradish-peroxidase-filled pipettes. Their receptive fields were mapped and classified as corresponding to those of parvi- or magnocellular neurons in the lateral geniculate nucleus. The axons were then impaled and injected intraaxonally with horseradish peroxidase. Two magnocellular (MA) and two parvicellular (PA) axons were successfully recovered and reconstructed in three dimensions. The two MA axons arborised mainly in layer 4C alpha, as did the two PA axons in layer 4C beta. Few collaterals formed varicosities in layer 6. Both MA axons had two large, elongated clumps of bouton (approx. 300-500 x 600-1,200 microns each) and a small clump. One PA axon had two clumps (each with a core appr. 200 microns in diameter); the other had only one (appr. 150-200 microns in axon had 1,380; one MA axon had 3,200 boutons; and those of the more extensive MA axon were not counted. The distribution of postsynaptic targets as well as the number of synapses per bouton has been established for a sample of 150 PA boutons and 173 MA boutons from serial ultrathin sections. The MA axons made on average 2.1 synapses per bouton compared to 1.79 for one PA axon and 2.6 for the other. The sample of boutons taken from the two physiological types of axons contacted similar proportions of dendritic spines (52-68%), shafts (33-47%), and somata (0-3%). The postsynaptic elements were further characterized by immunostaining for GABA. All postsynaptic perikarya and some of the dendrites (4.5-9.5% of all targets) were positive for the amino acid. Near the thalamic synapse GABA-negative dendritic shafts frequently contained lamellar bodies, an organelle identical in structure to spine apparatus. Dendritic shafts and spines postsynaptic to the thalamocortical boutons frequently received an adjacent synapse from GABA-immunoreactive boutons. The similarity between the magno-and parvicellular axons in their targeting of postsynaptic elements, including the GABAergic neurons, suggests that the structural basis of the physiological differences between 4C alpha and 4C beta neurons should be sought in other aspects of the circuitry of layer 4C, such as local cortical circuits, or in the far greater horizontal extent of the thalamocortical and GABAergic axons in layer 4C alpha compared to those in the beta subdivision.

Animals↗
PubMed1989

Physiological, morphological, and cytochemical characteristics of a layer 1 neuron in cat striate cortex.

We have recorded from a small neuron in layer 1 of the striate visual cortex in a 34-day-old kitten. It had a simple, orientation-selective receptive field that was nondirectional and showed length summation. The neuron was injected intracellularly with horseradish peroxidase. Computer-aided reconstruction revealed that it had a dense axonal plexus confined to layer 1, elongated in the anteroposterior dimension. By means of an antibody directed against a GABA-like antigen, and postembedding immunocytohemistry, the neuron was found to be strongly immunoreactive. The main input to soma and dendrites of the neuron was from synapses that were not GABA-L-immunoreactive, and probably originated from pyramidal cells. The axon of the cell formed synapses on dendritic shafts and spines, whose most likely sources were the apical tufts of pyramidal cell dendrites. These data suggest that such neurons may be involved in local circuits that contribute to the formation of pyramidal cell receptive fields.

Animals↗
PubMed1989

Development of Y-axon innervation of cortical area 18 in the cat.

1. Geniculocortical Y-axons (n = 38) in the optic radiations of 4-5-week-old kittens (n = 20) and adult cats (n = 18) were studied both physiologically and morphologically. Axons were recorded from intracellularly and subsequently filled ionophoretically with horseradish peroxidase (HRP). The HRP filled the axons' terminal arborizations in visual cortex (particularly well for those innervating area 18). Fourteen axons appeared to be completely filled with HRP (n = 8 in kitten, n = 6 in adult) and served as the basis for the quantitative analysis of the terminal arborizations reported in this study. 2. The distribution and correspondence of the axonal boutons to presynaptic elements in cortical layer 4A was analysed at both the light and electron microscope level using computerized three-dimensional analysis and serial section reconstruction, respectively. Compared to adult axons, the boutons of the kitten axons were smaller (means = 0.75 vs. 1.75 microns length, P less than 0.001) and more densely spaced both along individual axon branches (means = 6.60 vs. 11.20 microns interbouton interval, P less than 0.001) and between neighbouring branches of the same axon (means = 4.7 vs. 6.4 microns nearest-neighbour distance, P less than 0.01). 3. Most kitten boutons made a single Gray's type 1 synapse on a cortical neurone, unlike adult boutons which usually contacted two or more postsynaptic targets. Both kitten and adult axons had dendritic spines as their major target. Occasionally, HRP reaction-product was observed in cortical neurones postsynaptic to the labelled geniculocortical axon, which gave some estimate of the number of synaptic contacts between a single geniculocortical axon and target cell (about five). 4. The kitten Y-axons innervated the visual cortex in a pattern similar to that of the adult, with the richest terminal branching and bouton density in layer 4A with some additional boutons distributed in layers 3, 4B and 6. The extent of the terminal arborizations primarily in layer 4A (as measured in surface views) of kitten Y-axons in area 18 was significantly less than that of adult Y-axons in area 18 (means = 0.9 mm2 vs. means = 1.2 mm2, P = 0.04). 5. We conclude that between 4 and 5 postnatal weeks and 1 year, geniculocortical Y-axons projecting to cortical area 18 undergo four major changes. These include a reduction in synaptic bouton density (both in three-dimensional space and along individual branches), a concomitant moderate expansion in the surface area of cortex innervated, an increase in bouton size and an increase in the number of synaptic contacts made by each bouton. A general proportional growth of the individual axons' terminal arborization together with fusion and/or separation of neighbouring boutons is sufficient to explain this development.

Aging↗
PubMed1989

Closed intravenous administration of gonadotropin-releasing hormone: safety of extended peripheral intravenous catheterization.

The use of pulsatile gonadotropin-releasing hormone is an effective means of inducing ovulation, but requires prolonged intravenous (IV) or subcutaneous administration. We hypothesized that the use of self-contained infusion pumps using fluids maintained in a closed system would permit safe peripheral IV administration of gonadotropin-releasing hormone, and possibly other hormones, over prolonged intervals. Thirty-eight female patients undergoing pulsatile IV gonadotropin-releasing hormone therapy were followed for 1958 catheter days (230 catheters). Catheters were removed for signs of local inflammation, at the completion of a treatment episode or, initially, at routine intervals of 7-10 days. There were no episodes of fever (temperature over 37.5C) and three episodes of local inflammation. The incidence of significant catheter-tip cultures was 11%, and none were associated with local inflammation. There were four positive blood cultures (2%), none associated with local or systemic signs of infection. We conclude that the use of a closed system of prolonged peripheral IV cannulation is relatively safe when combined with fastidious care of the catheter site and careful outpatient monitoring for long-term administration of pulsatile gonadotropin-releasing hormone.

Adult↗
PubMed1988

Evidence for the connections between a clutch cell and a corticotectal neuron in area 17 of the cat visual cortex.

Evidence is presented for the synaptic connectivity between a physiologically characterized and intracellularly filled GABAergic interneuron and a corticotectal pyramidal neuron in area 17 of the cat visual cortex. The interneuron was located in layer 4 and had the morphological characteristics of a clutch cell. The physiological data demonstrated that the clutch cell received direct X-type innervation from the dorsal lateral geniculate nucleus. These results indicate that a GABAergic neuron is directly involved during the first cortical stages of geniculocorticotectal interactions. Furthermore, the proximal location of the clutch-cell inputs to the labelled dendrite suggests a strategic siting of intracortical feedforward inhibition.

Animals↗
PubMed1988

Selective responses of visual cortical cells do not depend on shunting inhibition.

Theoretical analyses of the electrical behaviour of the highly branched processes of nerve cells has focused attention on the possibility that single cells perform complex logical operations rather than simply summing their synaptic inputs. In particular, it has been suggested that the orientation and direction selectivity of cells in the visual cortex results from the action of a nonlinear 'shunting' inhibition that emulates an AND-NOT logical operation. The characteristic biophysical feature of this proposed inhibitory mechanism is that it evokes a large and relatively sustained increase in the conductance of the neuronal membrane while leaving the membrane potential unaffected. This shunting mechanism contrasts with linear 'summative' inhibition in which conductance changes are less prominent, and inhibition is achieved by hyperpolarization of the membrane potential. In a direct experimental test of the hypothesis that the selectivity of visual cortical neurons depends on shunting inhibition we found no evidence for the large conductance changes predicted by the theory.

Action Potentials↗
PubMed1988

The dorsal lateral geniculate nucleus of the sheep and its retinal connections.

Layers 1 and 2 of the sheep's LGN have similar properties to layers A and A1 in the cat. In layer 3 of the sheep the cell size is the same as that of the main group in layers 1 and 2, and it is contralaterally driven but has no sublamination. There is a medial interlaminar nucleus in the sheep which consists of two incomplete laminae, each driven by one eye. Scattered cells from the whole of the retina temporal to the decussation line project to the contralateral LGN. There is only a band of cells 1.5 mm wide nasal to the decussation line which project to the ipsilateral LGN. Cells with corresponding ipsilateral fields are found on the medial side of the nucleus in layers 1 and 2. A few cells with orientation sensitivity have been seen in the LGN. The area of the greatest cell density in the retina, the streak, is accommodated in the LGN by expansion vertically, not horizontally.

Animals↗
PubMed1987

Evidence for interlaminar inhibitory circuits in the striate cortex of the cat.

An interlaminar, ascending, and GABAergic projection is demonstrated in the striate cortex of the cat. We have examined a basket cell, with soma and smooth dendrites in layers V and VI, that was injected intracellularly with HRP in the kitten. Three-dimensional reconstruction of its axon revealed a horizontal plexus in layer V and upper VI, extending about 1.8 mm anteroposteriorly and 0.8 mm mediolaterally; a dense termination in the vicinity of the soma in layers V and VI; and an ascending tuft terminating in layers II and III in register above the soma and about 250 microns in diameter. Many boutons of this cell contacted neuronal somata and apical dendrites of pyramidal cells and subsequent electron microscopy showed that these boutons formed type II synaptic contacts with these structures. A random sample of postsynaptic targets (n = 199) in layers III, V, and VI showed that somata (20.1%), dendritic shafts (38.2%), and dendritic spines (41.2%) were contacted. The fine structural characteristics of postsynaptic elements indicated that the majority originated from pyramidal cells. Direct identification of postsynaptic neurons was achieved by Golgi impregnation of four large pyramidal cells in layer V, which were contacted on their somata and apical dendrites by between three and 34 boutons of the HRP-filled basket cell. Layer IV neurons were not contacted. Golgi-impregnated neurons similar to the HRP-filled basket cell were also found in the deep layers. The axonal boutons of one of them were studied; it also formed type II synapses with somata and apical dendrites of pyramidal cells. Boutons of the HRP-filled neuron were shown to be GABA-immunoreactive by the immunogold method. This is direct evidence in favour of the GABAergic nature of deep layer basket cells with ascending projections. The existence of an ascending GABAergic pathway was also demonstrated by injecting [3H]GABA into layers II and III. The labelled amino acid was transported retrogradely by a subpopulation of GABA-immunoreactive cells in layers V and VI, in addition to cells around the injection site. The axonal pattern and mode of termination of deep basket cells make them a candidate for producing or enhancing directional selectivity, a characteristic of layer V cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗