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Biomedical subjects

C M Leonard

Publications and source records attributed to C M Leonard.

At least 55 records · Page 3Linked to original sources
PubMed1987

Nuclear events during early chondrogenesis: phosphorylation of the precartilage 35.5-kDa domain-specific chromatin protein and its regulation by cyclic AMP.

During chondrogenesis in vivo and in vitro, a family of nonhistone proteins (Mr 35,500), designated PCP 35.5, is lost from the nuclei of precartilage mesenchyme cells. A basic subcomponent of this family, designated PCP 35.5b, is phosphorylated during the first few hours of chondrogenesis in vitro by a phosphorylating system whose activity is enhanced 12- to 15-fold by exposure of differentiating precartilage cells to dibutyryl cyclic AMP. This phosphorylating system is present in isolated precartilage cell nuclei, where it retains its dependence on cyclic AMP and its specificity for PCP 35.5b. Assays for nuclear cyclic AMP inhibitable protein phosphatase activity capable of dephosphorylating PCP 35.5b were negative, indicating that the system responsible for phosphorylating this protein is a cyclic AMP-dependent protein kinase. Chromatin fractionation studies indicate that PCP 35.5b is localized at sites previously shown to be closely associated with DNase I-sensitive domains of precartilage cell chromatin. These studies define PCP 35.5b as a strategically located component of precartilage cell chromatin which is the major or sole chromatin target of cyclic AMP-dependent phosphorylation during chondrogenesis. This chromatin modification occurs prior to overt cartilage differentiation and may therefore play a regulatory role in the acquisition of the cartilage cell phenotype.

Animals↗
PubMed1987

Functional subdivisions of the temporal lobe neocortex.

In order to gather evidence on functional subdivisions of the temporal lobe neocortex of the primate, the activity of more than 2600 single neurons was recorded in 10 myelo- and cytoarchitecturally defined subdivisions of the cortex in the superior temporal sulcus (STS) and inferior temporal gyrus of the anterior part of the temporal lobe of 5 hemispheres of 3 macaque monkeys. First, convergence of different modalities into each area was investigated. Areas TS and TAa, in the upper part of this region, were found to receive visual as well as auditory inputs. Areas TPO, PGa, and IPa, in the depths of the STS, received visual, auditory, and somatosensory inputs. Areas TEa, TEm, TE3, TE2, and TE1, which extend from the ventral bank of the STS through the inferior temporal gyrus, were primarily unimodal visual areas. Second, of the cells with visual responses, it was found that some neurons in areas TS-IPa could be activated only by moving visual stimuli, whereas the great majority of neurons in areas TEa-TE1 could be activated by stationary visual stimuli. Third, it was found that there were few sharply discriminating visual neurons in areas TS and TAa; of the sharply discriminating visual neurons in other areas, however, neurons that responded primarily to faces were found predominantly in areas TPO, TEa, and TEm (in which they represented 20% of the neurons with visual responses); neurons that were tuned to relatively simple visual stimuli such as sine-wave gratings, color, or simple shapes were relatively common in areas TEa, TEm, and TE3; and neurons that responded only to complex visual stimuli were common in areas IPa, TEa, TEm, and TE3. These findings show inter alia that areas TPO, PGa, and IPa are multimodal, that the inferior temporal gyrus areas are primarily unimodal, that there are areas in the cortex in the anterior and dorsal part of the STS that are specialized for the analysis of moving visual stimuli, that neurons responsive primarily to faces are found predominantly in areas TPO, TEa, and TEm, and that architectural subdivisions of the temporal lobe cortex are related to neuronal response properties.

Action Potentials↗
PubMed1986

Developmental changes in the astrocytic response to lateral olfactory tract section.

When the lateral olfactory tract (LOT) of the golden hamster, Mesocricetus auratus, is transected in the first week of postnatal life, axons can grow back past the lesion and achieve functional reinnervation of caudal projection regions. In contrast, when the tract is sectioned after postnatal day 7 (P7), axons do not reinnervate regions caudal to the cut. The experiments reported here investigated whether regenerative failure after tract section in pups older than P7 is accompanied by developmental changes in the astrocytic response. LOT transections were performed at P3 and P9 and the glial reaction was observed at survival times ranging from 12 hr to 2 weeks. Immunocytochemistry with glial fibrillary acidic protein (GFAP) was employed for histological visualization of astrocytic reactivity. Staining for GFAP immunoreactivity showed an appreciable glial reaction after tract section at both P3 and P9, but the extent of astrocytic hypertrophy and proliferation of glial processes was considerably greater and more extensive after tract section at P9. Radial glial cells were observed 2 weeks after LOT transection at P3 but were absent after lesions made at P9. The results from this study suggest that the developmental loss of regenerative capacity after LOT transection may be related to maturational changes in the glial response. In particular, the presence of radial glial elements after P3 lesions could serve to establish a more favorable microenvironment for axonal elongation.

Animals↗
PubMed1986

The terminal nerve projects centrally in the hamster.

The projections of the peripheral and intracerebral portions of the hamster terminal nerve were examined with lesion and immunocytochemical techniques. After transection, proximal processes of the terminal nerve accumulate luteinizing hormone-releasing hormone-immunoreactive material, while the distal processes disintegrate and are no longer stained. It thus becomes possible to determine the direction of conduction of terminal nerve axons. The results of transection at the level of the cribriform plate, along the olfactory bulb, and in the ventral forebrain were all consistent in indicating a centripetal direction of conduction. Immunoreactive material collected distal to the lesion at each of these levels. All peripheral lesions eliminated processes coursing into and through the terminal ganglion at the base of the ventral forebrain. These lesions left intact, however, the terminal ganglion projections to the accessory olfactory bulb and ventral forebrain. These results indicate a centripetal projection from terminal neurons in the nasal cavity, along the olfactory bulbs and within the terminal ganglion to successively more caudal levels. This suggests that neural messages are conveyed from nasal cavity to the brain through this route. Because immunoreactive fibers were found within the sensory epithelium of the vomeronasal organ a sensory and/or sensory modulatory action is suggested.

Afferent Pathways↗
PubMed1986

Acetylcholinesterase and luteinizing hormone-releasing hormone distinguish separate populations of terminal nerve neurons.

The terminal nerve is composed of a morphologically heterogeneous population of unipolar, bipolar and multipolar neurons located in the nasal and intracranial cavities of vertebrates. The question has arisen as to whether these neurons are neurochemically heterogeneous and therefore possibly functionally different as well. Among the substances localized in the terminal nerve are acetylcholinesterase and luteinizing hormone-releasing hormone-like immunoreactive material. We have developed a double-label procedure, combining immunocytochemistry and enzyme histochemistry to determine whether these two substances are localized within different populations of terminal nerve neurons. Compatibility of the two procedures was accomplished by modifications of the fixative and primary antibody solutions. In the immunocytochemical step, the avidin-biotin-peroxidase complex coupled to a new chromogen, Chromo-red, produced a bright red reaction product in neurons containing luteinizing hormone-releasing hormone-like material. This reaction product was easily differentiated from the black silver-intensified acetylcholinesterase label. In both neonatal and adult preparations, a large population of terminal neurons contained the acetylcholinesterase label only, whereas a smaller population contained both acetylcholinesterase and luteinizing hormone-releasing hormone-like material. The acetylcholinesterase-containing population of neurons was concentrated peripherally and included multipolar neurons. In contrast neurons with the two substances co-localized were unipolar or bipolar and were concentrated centrally. The simultaneous visualization of acetylcholinesterase and luteinizing hormone-releasing hormone-like material in the same tissue section enable the differentiation of two separate neurochemically defined populations of terminal neurons. The distribution of these two neuronal types was the same in neonatal and adult animals. These data provide support for a functional diversity of terminal neurons.

Acetylcholinesterase↗
PubMed1985

Selectivity between faces in the responses of a population of neurons in the cortex in the superior temporal sulcus of the monkey.

There is a population of neurons in the cortex in the middle and anterior part of the superior temporal sulcus (STS) of the monkey with responses which are selective for faces. If, consistent with the effects of damage to the temporal lobe, these neurons are involved in face recognition or in making appropriate social responses to different individuals, then it might be expected that at least some of these neurons might respond differently to different faces. To investigate whether at least some of these neurons do respond differently to different faces, their responses were measured to a standard set of faces, presented in random sequence using a video framestore. It was found that a considerable proportion of the neurons with face-selective responses tested (34/44 or 77%) responded differently to different faces, as shown by analyses of variance. An index of the discriminability of the most and least effective face stimulus (d') ranged between 0.2 and 5.0 for the different neurons. Although these neurons often responded differently to different faces, they did not usually respond to only one of the faces in the set, so that information that a particular face had been shown was present across an ensemble of neurons, rather than in the responses of an individual neuron. These findings indicate that the responses of these neurons would be useful in providing information on which different behavioral responses made to different faces could be based. These neurons could thus be filters, the output of which could be used for recognition of different individuals and in emotional responses made to different individuals.

Animals↗
PubMed1985

Role of low and high spatial frequencies in the face-selective responses of neurons in the cortex in the superior temporal sulcus in the monkey.

There are neurons in the cortex in the anterior part of the superior temporal sulcus of the macaque monkey with visual responses selective for faces. One aim of the present study was to analyze further the information which leads them to respond, by measuring their responses to parametrically filtered stimuli. The responses of 32 such single neurons were measured to faces which were digitized, lowpass filtered at spatial frequencies of 2, 4, 8,...128 cycles/face, highpass filtered at frequencies of 4, 8,...64 cycles/face, and presented in random sequence using a video framestore. It was found that many of the neurons could respond to blurred images of faces, with a mean frequency at half-maximum amplitude of the neuronal response to the series of lowpass filtered images of faces of 3.3 cycles/face. Almost all the neurons had lowpass cutoff frequencies defined in this way below 8 cycles/face. Many of the neurons could also respond to images of faces in which the only information remaining was a limited amount of high spatial frequency edge information. The mean frequency at half-maximum amplitude of the neuronal response to the series of highpass filtered images of faces was 29.7 cycles/face. Almost all the neurons had highpass cutoff frequencies above 8 cycles/face. Thus, many of the neurons could respond to a lowpass and a highpass filtered image of a face even when these had no spatial frequencies in common. The mean separation between the lowpass and highpass cutoff frequencies was 3.2 octaves. For comparison, face recognition in man can be performed with images which contain only information up to 8 cycles/face, or with highpass filtered images which contain only information down to 8 cycles/face. The response of the neurons was not always a smooth function of frequency, but could decrease as higher frequencies were included in the lowpass filtered images of faces, or as low frequencies were included in the highpass filtered images of faces. This indicates that information in certain frequency bands was able to inhibit these neurons. This was particularly likely to occur for the non-optimal face stimulus for a given neuron, indicating that the selectivity of these neurons to different faces was a combination of the excitation produced by some information in faces and inhibition produced by other.

Action Potentials↗
PubMed1985

Neurons in the amygdala of the monkey with responses selective for faces.

To investigate the functions of the amygdala in visual information processing and in emotional and social responses, recordings were made from single neurons in the amygdala of the monkey. A population of neurons (40 of more than 1000 recorded in 4 monkeys) was investigated which responded primarily to faces. These neurons typically (1) responded to some human or monkey faces, which were presented to the monkey through a large aperture shutter so that response latencies could be measured, or were simply shown to the monkey, (2) responded to 2-dimensional representations of these faces, as well as to real 3-dimensional faces, (3) had no responses or only small (less than half maximum) responses to gratings, simple geometrical, other complex 3-D stimuli, or to arousing and aversive stimuli, (4) had response latencies of 110-200 ms, (5) were located in the basal accessory nucleus of the amygdala, (6) responded differently to different faces, as shown by measures of d', and could thus over a population of such neurons code information useful for making different responses to different individuals, (7) could in some cases (9/11 tested) respond to parts of faces, and (8) in a few cases (4/19 tested) responded more to a face which produced an emotional response. A comparison made in three monkeys of the responses of these neurons with the responses of 77 neurons with face-selective responses recorded in the cortex of the superior temporal sulcus (STS) showed that the amygdaloid neurons had longer response latencies (110-200 compared to 90-140 ms), and were in some respects more selective in their responses to different faces. It is suggested that the deficits in social and emotional behavior produced by amygdala lesions could be due in part to damage to a neuronal system specialized in utilizing information from faces so that appropriate social and emotional responses can be made to different individuals.

Amygdala↗
PubMed1985

Esophageal speech: double-contrast evaluation of the pharyngo-esophageal segment.

Alaryngeal voice is usually accompanied by esophageal speech; however, about 40% of laryngectomy patients are unable to achieve adequate esophageal speech and must rely on mechanical devices for communication. A technique was developed for performing double-contrast studies of the hypopharynx, cervical esophagus, and pharyngo-esophageal segment using thick barium and the air normally injected for speech. Simultaneous audio and video recordings obtained during esophageal speech allowed correlation of the quality of speech with the motion of the pharyngo-esophageal segment. In 35 patients with various degrees of fluency in esophageal speech, normal and abnormal function of the pharyngo-esophageal segment was documented. Inadequate esophageal speech can be related to abnormal motion of the pharyngo-esophageal segment.

Contrast Media↗
PubMed1983

Early recovery of function after olfactory tract section correlated with reinnervation of olfactory tubercle.

Behavioral recovery and cortical reinnervation after early olfactory tract section were assessed in the infant golden hamster (Mesocricetus auratus). Hamster pups show strong thermotaxis at birth which declines abruptly after postnatal day (P) 8 in normal pups. Unilateral olfactory bulbectomy on P5 causes persistent thermotaxis through the second postnatal week. In this study, the bulb's output pathway, the lateral olfactory tract, was unilaterally severed on P5 and pup thermotaxis was tested through P15. Complete tract section, like bulbectomy, prolonged thermal responding beyond P8. In contrast to bulbectomy, however, some tract-sectioned pups showed recovery before P15 while others continued to show persistent thermotaxis throughout testing. The olfactory bulb projection was examined 10 days after tract section in order to determine whether recovery and persistent thermotaxis were associated with different patterns of cortical innervation. Eleven pups with complete transections showed recovery during the second week. In 10 of these pups, olfactory bulb fibers had penetrated the damaged region after surgery to reinnervate the olfactory tubercle. Three of these pups also exhibited some reinnervation of piriform cortex. The lesions of pups showing persistent thermotaxis were more severe, extending bilaterally or into deep cortical layers, and olfactory fibers had failed to reinnervate caudal terminal fields. All pups with olfactory tract sections showed extensive sprouting rostral to the cut, regardless of their behavioral profile. In no case had postlesion growth innervated the entorhinal or amygdaloid areas. Inhibition of thermotaxis was associated with reinnervation of the olfactory tubercle rather than more rostral, lateral or caudal olfactory cortex. We conclude that regrowth of olfactory tract fibers caudal to early transection is rapid and has functional consequences for early behavioral development.

Animals↗
PubMed1982

Developmentally regulated nonhistone proteins: evidence for deoxyribonucleic acid binding role and localization near deoxyribonuclease I sensitive domains of precartilage cell chromatin.

Differentiation of cartilage from precartilage mesenchyme in the chick embryo is accompanied by the loss of two abundant nonhistone proteins (Mr 35 500 and 125 000) termed PCP 35.5 and PCP 125. Here we examine the distribution of these and other developmentally regulated nonhistones in nuclease-sensitive regions of precartilage and cartilage chromatin. In particular, we show that PCP 35.5 is a tight DNA-binding protein that is localized near deoxyribonuclease I (DNase I) sensitive regions of precartilage chromatin. Localization of nonhistones was demonstrated by excising domains of precartilage chromatin with DNase II which are simultaneously highly enriched in PCP 35.5, in PCP 125, and DNase I sensitive DNA sequences. These domains comprise at least 25% of the cell's DNase I sensitive sequences, as well as small DNase I resistant regions with which the two nonhistones are associated. These findings suggest that PCP 35.5 (and possibly PCP 125) may play a developmentally regulated role nearby DNase I sensitive domains of the cartilage progenitor cell chromatin.

Animals↗
PubMed1982

Developmental changes in the topographical distribution of cells contributing to the lateral olfactory tract.

Developmental changes in the locations of cells in the olfactory bulb which contribute axons to the lateral olfactory tract (LOT) were investigated using retrograde transport of horseradish peroxidase (HRP). HRP was placed in the olfactory tubercle, LOT, and/or piriform cortex of golden hamsters aged 3,7,8 and 20 days. The numbers of labeled mitral and tufted cells were counted on equidistant sections through the olfactory bulb. In the younger animals (days 3 and 7), there was a distinct localization of labeled cells in the medial quadrant of the bulb. In the 3-day-old group 49% of all labeled cells were located in the medial quadrant, but by day 8 the per cent of cells in all 4 quadrants was equivalent. Between days 3 and 20, the average perimeter of the mitral cell layer doubled. There was a similar increase in the average relative total number of labeled cells per bulb. When pairs of brains from the different age groups with HRP placements of similar size and location were compared, the older brain always had more labeled cells. There was no relation of the number or distribution of labeled cells to the location of the injection. The number of labeled cells correlated positively with the size of the injection within each age group. We believe this is the first report of a developmental topographical gradient of the cells of origin of the LOT. This localization may be related to early topographical differences in functional activity which reflect a limited exposure to odors in the first week of life.

Animals↗
PubMed1982

Shifting strategies for behavioral thermoregulation in developing golden hamsters.

Developmental changes in the golden hamster pup's capacity for behavioral temperature regulation were studied. Groups of three pups aged 4-14 days were tested at room temperature (22 degrees C), on a strong gradient (34-22 degrees C), and on a mild gradient (30-22 degrees C). The proportion of time engaged in the following behaviors was recorded: contact with the warm edge (thermotaxis), active huddling, and quiet huddling. Pups tested at 22 degrees C engaged in active huddling, and their temperature dropped rapidly. Only on Day 14 were they able to maintain their temperature constant with a combination of vigorous exploration and quiet huddling. On the strong gradient, by contrast, pups were able to regulate their temperature at all ages. Young pups (4-5 days) depended on thermotaxis rather than huddling, separating when their temperature started to rise. With age, quiet huddling replaced thermotaxis as a dominant behavior. On the mild gradient, pups combined active and quiet huddling with thermotaxis, so that their temperature dropped at al slow steady rate (.1 degrees C/min). It is concluded that hamster pups have a well-developed capacity for behavioral temperature regulation. Whether they attempt to keep their temperature constant or tolerate a slow rate of drop depends on the amount of exogenous heat available, which under natural conditions would be supplied predominantly by the mother. These results suggest that the pups as well as the mother may participate in thermal regulation in the nest.

Aging↗
PubMed1980

Successful silver impregnation of degenerating axons after long survivals in the human brain.

Degenerating axons in the human brain were successfully impregnated with reduced silver methods. The appearance of degenerating fibers did not differ markedly with survival times of three weeks and two, six, and twelve years following cerebral infarction or contusion of the brain. Impregnated fibers were found only along the appropriate corticofugal pathways. Electron microscopic examination of Vibratome-cut, silver-stained sections demonstrated silver deposition almost exclusively within axon fragments. Previous studies using anterograde degeneration methods in the human brain have limited their choice of cases to those with short periods of survival. Relaxing the restriction of short survival times extends the range of cases which can be used to study neural connections which may be unique to, or different in, the human brain.

Axons↗
PubMed1978

Maturational loss of thermotaxis prevented by olfactory lesions in golden hamster pups (Mesocricetus auratus).

Five-day-old golden hamster pups were tested preoperatively on a thermal gradient, subjected to bilateral or unilateral olfactory bulbectomy or control dorsal cortical removal, and then tested on Days 6-15. Locomotion and rectal or belly temperature were monitored throughout the 2-min test. Control pups became quiescent in the hot end of the gradient on Days 5-7 but after Day 8 chose cooler regions and increased their activity. Both unilaterally and bilaterally bulbectomized pups spent more time in the heat throughout testing. They were also less active and allowed their temperature to rise more rapidly than controls. Percentage of time in the heat was elevated in all bulbectomized pups, although some retained the ability to make an olfactory discrimination. Enhanced thermal behavior is apparently not due to anosmia per se. Altered thermal perception or responsitivity may result from loss of "nonspecific" olfactory projections that normally would mature at the beginning of the second week.

Animals↗