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C M Leonard

Publications and source records attributed to C M Leonard.

At least 37 records · Page 2Linked to original sources

Pars triangularis asymmetry and language dominance.

The pars triangular is a portion of Broca's area. The convolutions that form the inferior and caudal extent of the pars triangularis include the anterior horizontal and anterior ascending rami of the sylvian fissure, respectively. To learn if there are anatomic asymmetries of the pars triangularis, these convolutions were measured on volumetric magnetic resonance imaging scans of 11 patients who had undergone selective hemispheric anesthesia (Wada testing) to determine hemispheric speech and language lateralization. Of the 10 patients with language lateralized to the left hemisphere, 9 had a leftward asymmetry of the pars triangularis. The 1 patient with language lateralized to the right hemisphere had a significant rightward asymmetry of the pars triangularis. Our data suggest that asymmetries of the pars triangularis may be related to speech-language lateralization.

Adolescent↗

Quantified volumes of temporal lobe structures in patients with epilepsy.

The T1-weighted volumetric magnetic resonance images of 31 patients with intractable temporal lobe epilepsy, and 13 control subjects matched for age and sex, were subjected to semiautomated threshold analysis. The method used proved to be relatively fast and reliable. An index of temporal lobe interhemispheric asymmetry was extracted by thresholding high-signal (white matter) pixels. Patients had significantly more asymmetrical indices for white matter and hippocampal volumes that did control subjects, and the two indices were significantly correlated, providing evidence for the validity of the white matter index. Differences in both indices were consistent with decreased tissue on the side of the focus. In classification analyses a combination of these two indices correctly predicted the side of focus at a greater rate than did either used alone. Findings provide support for the hypothesis that seizure activity is associated with atrophy in both mesial and lateral temporal lobe structures.

Adult↗

Magnetic resonance imaging of cerebral anomalies in subjects with resistance to thyroid hormone.

OBJECTIVE: Resistance to thyroid hormone (RTH) is an autosomal dominant disease caused by mutations in the human thyroid receptor beta gene on chromosome 3. Individuals with RTH have an increased incidence of attention deficit hyperactivity disorder (ADHD). The purpose of this study was to search for developmental brain malformations associated with RTH. METHOD: Forty-three subjects (20 affected males [AM], 23 affected females [AF]) with resistance to thyroid hormone and 32 unaffected first degree relatives (18 unaffected males [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric acquisition that provided 90 contiguous 2 mm thick sagittal images. Films of six contiguous images beginning at a standard sagittal position lateral to the insula were analyzed by an investigator who was blind with respect to subject characteristics. The presence of extra or missing gyri in the parietal bank of the Sylvian fissure (multimodal association cortex) and multiple Heschl's transverse gyri (primary auditory cortex) were noted. RESULTS: There was a significantly increased frequency of anomalous Sylvian fissures in the left hemisphere in males with RTH (AM: 70%; AF: 30%; UM: 28% UF: 28%). Also, there was an increased frequency of anomalous Sylvian fissures on the left combined with multiple Heschl's gyri in either hemisphere in males with RTH (AM: 50%; AF: 9%; UM: 6%; UF: 0%). However, RTH subjects with anomalies did not have an increased frequency of ADHD as compared with RTH subjects with no anomalies. CONCLUSIONS: Abnormal thyroid hormone action in the male fetus early during brain development may be associated with grossly observable cerebral anomalies of the left hemisphere. The effects of mutations in the thyroid receptor beta gene provide a model system for studying the complex interaction of genetic and nongenetic factors on brain and behavioral development.

Adolescent↗

Morphologic cerebral asymmetries and handedness. The pars triangularis and planum temporale.

OBJECTIVE: To explore the relationship between morphologic cerebral asymmetries of the pars triangularis (PTr) and the planum temporale (PT) measured on three-dimensional, gradient-echo, magnetic resonance imaging scans of healthy right- and left-handed subjects. DESIGN: (Blinded) comparison of healthy right- and left-handed subjects who underwent magnetic resonance imaging. SETTING: The Seimens 1-T Magnetom (Seimens, Iselin, NH) at the University of Florida Health Science Center, Gainesville. SUBJECTS: Healthy right-handed (n = 8) and left-handed (n = 8) subjects matched for age, sex, and educational level. MAIN OUTCOME MEASURES: (1) Average length of the PTr (anterior ascending and anterior descending rami), (2) average length of the PT, (3) asymmetry quotients ([left-right]/[(left+right) (0.5)]) of the PTr and PT, and (4) combined asymmetry quotients of the PTr and PT. RESULTS: There was a significant leftward asymmetry of the PTr and PT in the right-handed subjects, but there was no significant asymmetry in the left-handed subjects. When the combined asymmetry quotient of the PTr and PT was calculated, the right-handed subjects had a leftward asymmetry (87.5% [n = 7]) or left was equal to right (12.5% [n = 1]), and the left-handed subjects had a leftward asymmetry (62.5% [n = 5]), left was equal to right (12.5% [n = 1]), or a rightward asymmetry (25% [n = 2]). In the left-handed subjects, writing posture seemed to predict these combined asymmetry quotients, ie, left-handed subjects using an inverted writing posture had a leftward asymmetry and left-handed subjects using a non-inverted writing posture had a rightward asymmetry of the perisylvian speech-language regions. CONCLUSIONS: On three-dimensional, gradient-echo, magnetic resonance imaging scans, we found a significant leftward asymmetry of the PTr and PT. When the groups were divided into right- and left-handed subjects, the former had a significant leftward asymmetry of the PTr and PT, while the latter did not. Measurements of the PTr and PT appear to be important indexes of the known functional asymmetries of the perisylvian speech-language regions.

Adult↗

Planum temporale asymmetry and language dominance.

Language is lateralized to the left hemisphere in most individuals, and leftward asymmetry of the planum temporale has been reported in postmortem and imaging studies. In this study we measured the planum temporale on magnetic resonance imaging (MR) scans of patients (11 right-handers, 1 non-right-hander) who had selective hemispheric anesthesia or Wada testing performed for language lateralization. All subjects who had language lateralized to the left hemisphere (11 right-handers) had a leftward asymmetry of the planum temporale. One subject who had language lateralized to the right hemisphere (non-right-hander) had a strong rightward asymmetry of the planum temporale. These data suggest that planum temporale asymmetries determined by MR are associated with language dominance and may predict language laterality.

Adolescent↗

Neuronal responses in the ventral striatum of the behaving macaque.

To analyse the functioning of the ventral striatum, the responses of more than 1,000 single neurons were recorded in a region which included the nucleus accumbens and olfactory tubercle in 5 macaque monkeys. While the monkeys performed visual discrimination and related feeding tasks, the different populations of neurons found included neurons which responded to novel visual stimuli; to reinforcement-related visual stimuli such as (for different neurons) food-related stimuli, aversive stimuli, or faces; to other visual stimuli; in relation to somatosensory stimulation and movement; or to cues which signalled the start of a task. The neurons with responses to reinforcing or novel visual stimuli may reflect the inputs to the ventral striatum from the amygdala and hippocampus, and are consistent with the hypothesis that the ventral striatum provides a route for learned reinforcing and novel visual stimuli to influence behaviour.

Amygdala↗

Angelman and Prader-Willi syndrome: a magnetic resonance imaging study of differences in cerebral structure.

Recent improvements in magnetic resonance imaging techniques now allow the developing brain to be visualized in sufficient detail to perform "in vivo neuropathology." In this study we compared the cortical morphology in six children with Angelman and four with Prader-Willi syndrome. These two syndromes are of special interest because, although they are both caused by deletions in the same region of chromosome 15, Angelman children are far more severely affected, and do not speak. We measured the length of the banks of the Sylvian fissure in a gapless series of thin sagittal images. Angelman children had a significantly larger proportion (75%) of anomalous fissures than the Prader-Willi children (12%). Anomalous cortical growth could result from mistimed expression and recognition of macromolecules involved in axonal guidance, target recognition, and pruning. We hypothesize that misrouting of long projection axons may be related to the Sylvian fissure anomalies and the language disorder in Angelman syndrome.

Angelman Syndrome↗

Anomalous cerebral structure in dyslexia revealed with magnetic resonance imaging.

OBJECTIVE: To develop quantitative methods for identifying cerebral anomalies on magnetic resonance images of subjects with language disorders and other learning disabilities. DESIGN: Partially blinded comparison of subjects with dyslexia, unaffected relatives, and a control group balanced for age and socioeconomic status. Criterion standard: clinical diagnosis of dyslexia by physician or learning disabilities specialist on the basis of clinical assessment and family history. SETTINGS: Hospital pediatric neurology clinic and private reading clinic. PATIENTS AND OTHER PARTICIPANTS VOLUNTEERS: individuals with dyslexia (seven male and two female, aged 15 to 65 years) from professional families; unaffected first- and second-degree relatives (four male and six female, aged 6 to 63 years) available in the geographical area; and controls (five male and seven female, aged 14 to 52 years). INTERVENTIONS: Gradient echo three-dimensional scan in Seimens 1-Tesla Magnetom; 128 1.25-mm consecutive sagittal images. MAIN OUTCOME MEASURES: (1) Average length of the temporal (T) and parietal (P) banks of the planum temporale; (2) interhemispheric coefficients of asymmetry for T and P banks: Left-Right interhemispheric coefficients of asymmetry = (L-R)/[(L+R)/2]; (3) intrahemispheric coefficients of asymmetry = (T-P)/[(T+P)/2]; and (4) qualitative assessment of gyral variants in the parietotemporal operculum. RESULTS: All groups had left-sided asymmetry for the temporal bank and right-sided asymmetry for the parietal bank. The group with dyslexia had exaggerated asymmetries, owing to a significant shift of right planar tissue from the temporal to parietal bank. They also had a higher incidence of cerebral anomalies bilaterally (subjects with dyslexia, six of nine; relatives, two of 10; and controls, zero of 12). CONCLUSIONS: Quantitative assessment of high-resolution magnetic resonance images can reveal functionally relevant variations and anomalies in cerebral structure. Further refinement of these measurement techniques should improve the diagnosis, classification, and treatment of language disorders and other learning disabilities.

Adolescent↗

Activation of a heparin-degrading enzyme by a 'protein matrix' effect.

An unusual activating effect of protein on Flavobacterium heparinase is described. The phenomenon is nonselective with respect to protein species, but does not occur with other biomolecules such as nucleic acids, polysaccharides, or free amino acids. We show that protein activates heparinase over broad ranges of temperature and ionic strength, and stabilizes the enzyme against both reversible and irreversible structural changes. The nonselective activation of an inducible enzyme by protein may be an important regulatory mechanism in microenvironments in which the concentration of organic material may vary.

Bacterial Proteins↗

Altered precision grasping in stumptail macaques after fasciculus cuneatus lesions.

Patterns of precision grasp are described in stumptail macaques (Macaca arctoides) before and after lesions of the fasciculus cuneatus (FC). Three monkeys were videotaped while reaching for and grasping small food items. From these videotapes, records were made of the style and outcome of each grasp. Kinematic measurements were also made to describe grip formation and terminal grasp. During grip formation, grip aperture was measured as the distance between the tips of the index finger and the thumb. For terminal grasp, the joint angles of the index finger were measured. The majority of grasps by normal monkeys were of the precision type, in which the item was carried between the tips of the index finger and thumb. Each normal monkey approached objects with a highly consistent grip formation; that is, the fingertips formed a small grip aperture during the approach, and the aperture varied little on repeated grasps. To grasp an item, the forefinger moved in a multiarticular pattern, in which the proximal joint flexed and the distal joint extended. As a result of this combination of movements, the forefinger pad was placed directly onto the object. Following FC transection, the monkeys were studied for 10 months, beginning 1 month after the lesion, to allow for recovery from the acute effects of surgery. The monkeys could grasp the food items, but they rarely opposed the fingertips in precision grasp. Grip formation was altered and was characterized either by excessive grip aperture or by little to no finger opening. All of the monkeys used the table surface to help grasp items. Combined multiarticular patterns of flexion and extension were never observed postoperatively; they were replaced by flexion at all joints of the fingers. These results suggest that the FCs are more important for precision grasping than for other, less refined grasp forms (e.g., power grasps; Napier, 1956). The FCs provide critical proprioceptive feedback to cerebral areas involved in the planning and/or the execution of these movements.

Afferent Pathways↗

Alterations of natural hand movements after interruption of fasciculus cuneatus in the macaque.

As part of a series of investigations on the control of fine finger movements in the macaque, spontaneous use of the hand in grooming, scratching, and manipulation was observed before and after interruption of fasciculus cuneatus (FC). Videotaped observations were made of four stumptail macaques (Macaca arctoides) living outdoors in social groups. The monkeys were followed for 1 to 3 years postoperatively. For the first 2 weeks following surgery, all monkeys neglected the affected hand and did not use it for support, locomotion, climbing, scratching, foraging, or grooming. Recovery of gross arm and hand movements occurred over a 1- to 3-month period. All the monkeys eventually used the hand for support, climbing, and object manipulation, but fine control of the fingers did not recover. Also, there was an apparent hypotonia of the fingers, imparting a "floppy" appearance to the hand. The animals coped with the loss of fine control by decreasing the frequency of some behaviors, eliminating others, and developing alternative strategies. Exploratory movements that were utilized for investigating the anogenital area or foraging for small food items were eliminated by FC interruption. There were obvious deficits in grip formation and grasp of small food objects (see Glendinning et al., this issue), but effects on similar movements during grooming only became obvious after repeated inspection of videotaped records. Self-scratching and sweeps of the hand in grooming were preserved but altered in form and frequency. The component movements in these behaviors were relatively uncoordinated, and the fingers were splayed (abducted). Often the hand was formed in a rigid posture throughout the sweeping motion, and the fingers did not stroke the skin individually. Frame-by-frame analysis of videotapes revealed that the morphology of the precision grip during grooming, in movements termed "plucks," was permanently altered. Preoperatively, the monkeys kept the index finger and thumb closely apposed and routinely made contact on the distal surfaces of the digits, as has been described for precision grip in humans. Postoperatively, this relationship was altered. The index finger frequently missed the thumb tip and made contact on the proximal part of the phalanx, or missed the thumb altogether. Thus, the dorsal column input is important for proprioceptive guidance of movements that achieve "tactile foveation," when objects or surfaces are actively contacted by the receptive areas of keenest sensitivity (on the fingertips).

Afferent Pathways↗

Comparative neuroanatomy of the sexually dimorphic hypothalamus in monogamous and polygamous voles.

In the present work we evaluated the degree of sexual dimorphism in two cell groups of the medial preoptic-anterior hypothalamus (MPOA-AH) in monogamous and polygamous voles. Quantitative determinations were made of volume, cell number, and cell density for the anteroventral-periventricular nucleus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN-POA). Polygamous montane voles (Microtus montanus) had a greater degree of sexual dimorphism in both cell groups than did monogamous prairie voles (M. ochrogaster). Most notable was the complete absence of the AVPV in male montane voles; male montane voles also had a significantly larger SDN-POA volume than did females. The only sexual dimorphism in prairie voles was a greater cell density in the female AVPV. In addition, prairie voles had larger relative brain size than did montane voles. Comparative behavioral studies have revealed a correlation between the degree of sexual dimorphism in external morphology and mating system, i.e., polygamous species display greater levels of dimorphism than do monogamous species. The present results indicate that the effects of sexual selection can also be seen in those brain regions, like the hypothalamus, that underlie social and reproductive behavior. Moreover, these results support the hypothesis that neuroanatomic dimorphisms in the MPOA-AH may be related to sex differences in behavior.

Animals↗

Role of transforming growth factor-beta in chondrogenic pattern formation in the embryonic limb: stimulation of mesenchymal condensation and fibronectin gene expression by exogenenous TGF-beta and evidence for endogenous TGF-beta-like activity.

The possible role of TGF-beta-like molecules in skeletal pattern formation in the embryonic vertebrate limb was studied by analyzing the mechanism of enhancement of chondrogenesis in chick wing bud mesenchyme in vitro and testing for the presence and distribution of endogenous TGF-beta-like activity in this tissue. Transient exposure (3-6 hr) to TGF-beta 1 (1-2 ng/ml) on the day after plating resulted in a 1.5- to 2-fold enhancement of accumulation of Alcian blue (pH 1.0)-stainable extracellular matrix 5 days later. The enhancement of differentiation was preceded by an acceleration and an increase in the extent of precartilage condensation formation, visualized by Hoffman Modulation Contrast microscopy a day after TGF-beta treatment. In contrast, neither condensation nor subsequent chondrogenesis was stimulated by transient treatment with TGF-beta 1 on the day of plating. The effectiveness of a TGF-beta treatment regimen in enhancing chondrogenesis was correlated with its effectiveness in stimulating condensation formation. Exposures to the factor for 3-6 hr on the day after plating, which most consistently stimulated both condensation formation and chondrogenesis, also corresponded to a peak in the enhancement of the steady-state level of fibronectin mRNA (fourfold to eightfold over control levels) measured at the end of the treatment period. The elevation in fibronectin mRNA levels brought about by this treatment persisted throughout the period of condensation. Endogenous TGF-beta-like activity was detected in limb mesenchyme: extracts of freshly isolated and cultured limb tissues contained 6-25 pg TGF-beta-like activity per 1 x 10(6) cells by the Mv1Lu cell proliferation inhibition assay, and indirect immunofluorescence using a polyclonal antibody directed against a TGF-beta-related peptide indicated a patchy distribution of endogenous TGF-beta-like reactivity within a day after culture. These findings are discussed in relation to the "fibronectin prepattern" hypothesis for limb pattern formation.

Animals↗

Abnormal ambient glucose levels inhibit proteoglycan core protein gene expression and reduce proteoglycan accumulation during chondrogenesis: possible mechanism for teratogenic effects of maternal diabetes.

Using a tissue culture system based on a nearly pure population of avian precartilage mesenchymal cells, we have found that ambient glucose levels as little as 50% lower, or 100% higher, than normally present in embryonic sera are deleterious to cartilage development, as measured by the accumulation of highly sulfated proteoglycan and the corresponding cartilage-specific chondroitin sulfate core protein mRNA. Abnormal glucose concentrations in the ranges studied did not selectively influence cell replication, and the effects on chondrogenesis were not due to differences in overall protein synthesis or glucose utilization in the treatment groups. Core protein gene expression was more severely affected than accumulation of extracellular product, suggesting the existence of posttranscriptional compensatory mechanisms. The sensitivity to ambient glucose levels of both expression of the cartilage-specific chondroitin sulfate core protein gene and the accumulation of the corresponding extracellular matrix macromolecules during chondrogenesis suggest a molecular mechanism for the well-known adverse effect of maternal diabetes on embryonic skeletogenesis. The results further suggest that hypoglycemia resulting from stringent control of diabetes may also be deleterious to skeletal development.

Aggrecans↗

Metallothionein mRNA expression in mice homozygous for chromosomal deletions around the albino locus.

Deletions in chromosome 7 of the mouse affect the expression of the metallothionein gene Mt-1, which maps on chromosome 8, and steady-state levels of Mt-1 mRNA are reduced to 15-40% of normal in livers of newborn mice homozygous for either the c3H or c14CoS deletion. Glucocorticoids fail to induce hepatic Mt-1 mRNA levels in deletion homozygotes in contrast to normal littermates. However, zinc chloride is effective in inducing Mt-1 mRNA levels in livers of deletion homozygotes as well as of their normal littermates. Other tissues (e.g., kidney and intestine) of deletion homozygotes express basal levels of Mt-1 mRNA higher than those of normal littermates. In the intestine these are furthermore inducible by both hormonal and metal agents. Thus, loss of inducibility of the Mt-1 gene in deletion homozygotes concerns glucocorticoids only and is furthermore restricted to specific cell types (i.e., hepatocytes). The trans-acting factor(s) normally encoded in the deleted region of chromosome 7 appears to be instrumental in conferring on the metallothionein gene in hepatocytes the essential competence to respond to hormonal inducing signals.

Albinism↗

Developmental regulation of constitutive and inducible expression of hepatocyte-specific genes in the mouse.

Deletions in chromosome 7 of the mouse have been shown to cause failure of expression of certain liver-specific enzymes in newborn deletion homozygotes. Among these enzymes are L-tyrosine:2-oxoglutarate aminotransferase (EC 2.6.1.5) and phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lase (transphosphorylating); EC 4.1.1.32]. The studies reported here show that in fetal stages constitutive expression of the relevant genes on the level of steady-state mRNA is identical in the livers of homozygous deletion mutants and normal littermates. Furthermore, prenatally these enzymes are expressed also in cell types other than hepatocytes. Thus, the putative trans-acting regulatory factors encoded in the deleted region of chromosome 7 of the mouse appear to be concerned specifically with the regulation of cell type-specific inducible expression of various hepatocyte-specific genes, whereas constitutive expression of the same genes is not affected.

Animals↗

Terminal nerve damage impairs the mating behavior of the male hamster.

We examined the effects of bilateral terminal nerve (TN) transections (TNx) on the sexual behavior of male hamsters. These lesions produced a decrease in mating frequency and/or an increase in the number of intromissions required to reach ejaculation. Damage to the olfactory bulbs or rostral forebrain did not account for these effects. No amelioration of the behavioral impairments occurred over the mating sessions. Basal testosterone levels in the blood of male hamsters were not altered by TN damage. Hamsters with TNx retained their ability to detect odors, but demonstrated reduced attraction to vaginal odors as compared with unoperated animals. The reduced attraction to vaginal odors was most pronounced in sporadically mating TNx animals. These data suggest that the TN may facilitate odor-induced sexual excitation in the male hamster.

Animals↗